The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform
Manuel Sánchez - One of the best experts on this subject based on the ideXlab platform.
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Role of Polyamines and cAMP-dependent Mechanisms on 5α-dihydrotestosterone-elicited Functional Effects in Isolated Right Atria of Rat
Journal of cardiovascular pharmacology, 2009Co-Authors: Manuel Sánchez, Lorena Secades, Carmen Bordallo, José M. Rubín, Begoña Cantabrana, Clara Meana, Javier BordalloAbstract:Abstract Androgens produce acute vasodilation of systemic, pulmonary, and coronary arteries in several mammal preparations and increase cardiomyocyte contractility. A decrease of the spontaneous beating of sinoatrial cells has also been described. The aim of this study was to characterize the direct effect of 5alpha-dihydrotestosterone on the spontaneous chronotropism and Inotropism in the same preparation as an approach to establish the effect on cardiac output and their mechanism of action. The effects were studied on isolated right atria of Wistar rats placed in an organ bath in Tyrode solution at 37 degrees C and bubbled with carbogen. In male rats, the acute administration of 5alpha-dihydrotestosterone, a nonaromatizable derivate of testosterone, elicited a positive Inotropism, which was associated with a negative chronotropism. As reported in the left atria, polyamines and beta-adrenoceptors played a role in 5alpha-dihydrotestosterone-elicited positive Inotropism because the effect was antagonized by alpha-difluoromethylornithine, an inhibitor of polyamine synthesis, and atenolol, a beta1-adrenoceptor blocker, but not on the negative effect on chronotropism. The androgen increased the sinoatrial node recovery time, suggesting an effect on the mechanisms of spontaneous diastolic depolarization involved in atria pacemaking. These effects of 5alpha-dihydrotestosterone are not hormonally regulated because they are similarly produced in estrogenized females and gonadectomized male and female rats. These results suggest that the androgen could acutely improve cardiac performance.
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Putrescine modulation of acute activation of the beta-adrenergic system in the left atrium of rat.
European journal of pharmacology, 2008Co-Authors: Carmen Bordallo, Lucía Velasco, Lorena Secades, Javier Bordallo, Begoña Cantabrana, Clara Meana, Miriam Méndez, Manuel SánchezAbstract:Endogenous polyamines mediate acute metabolic effects and cardiac hypertrophy associated to beta-adrenoceptor stimulation. The aim of this study is to characterize the role of polyamines on beta-adrenoceptor system mediated responses. To this end, the functional interaction of polyamine modifying drugs on isoproterenol-elicited cardiotonic effect, in isolated left atria of male Wistar rats, and their effects on [(3)H]dihydroalprenolol (DHA) binding on beta-adrenoceptors and on adenylyl cyclase activity of membrane heart were studied. Polyamines interact with beta-adrenoceptors in rat heart, as shown by the displacement of [(3)H]DHA binding. Furthermore, putrescine (but not spermidine or spermine) increased adenylyl cyclase activity, elicited a positive Inotropism and increased intracellular cAMP. The putrescine effect on adenylyl cyclase was not antagonized by the beta-adrenoceptors blockers, alprenolol and ICI-118,551, and facilitated the isoproterenol effect. Neither alprenolol, atenolol nor ICI-118,551 antagonized putrescine-elicited positive Inotropism. However, the effect was abolished in preparations with desensitized beta-adrenoceptors. alpha-Difluoromethylornithine, an inhibitor of ornithine decarboxylase, antagonized the effect of isoproterenol on Inotropism and cAMP increase. In addition, putrescine might elicit effects by mechanisms independent of beta-adrenoceptor system, since in left atria with functional desensitized receptors an interaction with ouabain-elicited cardiotonic effect was observed. These results suggest that putrescine may act as a low affinity agonist on beta-adrenoceptors and modulate acute responses mediated by beta-adrenoceptors. These findings may be of importance in the physiology and in diseases involving cardiac beta-adrenoceptors.
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Putrescine modulation of acute activation of the β-adrenergic system in the left atrium of rat
European Journal of Pharmacology, 2008Co-Authors: Carmen Bordallo, Lucía Velasco, Lorena Secades, Javier Bordallo, Begoña Cantabrana, Clara Meana, Miriam Méndez, Manuel SánchezAbstract:Abstract Endogenous polyamines mediate acute metabolic effects and cardiac hypertrophy associated to β-adrenoceptor stimulation. The aim of this study is to characterize the role of polyamines on β-adrenoceptor system mediated responses. To this end, the functional interaction of polyamine modifying drugs on isoproterenol-elicited cardiotonic effect, in isolated left atria of male Wistar rats, and their effects on [3H]dihydroalprenolol (DHA) binding on β-adrenoceptors and on adenylyl cyclase activity of membrane heart were studied. Polyamines interact with β-adrenoceptors in rat heart, as shown by the displacement of [3H]DHA binding. Furthermore, putrescine (but not spermidine or spermine) increased adenylyl cyclase activity, elicited a positive Inotropism and increased intracellular cAMP. The putrescine effect on adenylyl cyclase was not antagonized by the β-adrenoceptors blockers, alprenolol and ICI-118,551, and facilitated the isoproterenol effect. Neither alprenolol, atenolol nor ICI-118,551 antagonized putrescine-elicited positive Inotropism. However, the effect was abolished in preparations with desensitized β-adrenoceptors. α-Difluoromethylornithine, an inhibitor of ornithine decarboxylase, antagonized the effect of isoproterenol on Inotropism and cAMP increase. In addition, putrescine might elicit effects by mechanisms independent of β-adrenoceptor system, since in left atria with functional desensitized receptors an interaction with ouabain-elicited cardiotonic effect was observed. These results suggest that putrescine may act as a low affinity agonist on β-adrenoceptors and modulate acute responses mediated by β-adrenoceptors. These findings may be of importance in the physiology and in diseases involving cardiac β-adrenoceptors.
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Role of Putrescine on Androgen-Elicited Positive Inotropism in the Left Atrium of Rats
Journal of cardiovascular pharmacology, 2008Co-Authors: Lucía Velasco, Agustín Hidalgo, Majoségarcía De Boto, Lorena Secades, Carmen Bordallo, Javier Bordallo, José M. Rubín, Begoña Cantabrana, Manuel SánchezAbstract:Functional and biochemical studies were performed in isolated left atria of male Wistar rats to study whether endogenous polyamines may mediate androgen-elicited positive Inotropism and their relationship with a rise in cAMP during the cardiotonic effect. 5 alpha-Dihydrotestosterone (100 microM) exposure increased intracellular putrescine as determined by HPLC, but it did not increase spermidine and spermine. This effect was antagonized by an inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine (10 mM), suggesting enzyme activation. alpha-Difluoromethylornithine also antagonized androgens-elicited Inotropism and the increase in intracellular cAMP. Putrescine (1 to 10 mM) elicited a concentration-dependent positive Inotropism associated with the cAMP increase. The prior incubation with putrescine antagonized 5 alpha-dihydrotestosterone-elicited Inotropism and did not produce sinergism on intracellular cAMP. Short-term incubation with 5 alpha-dihydrotestosterone or forskolin shifted to the left the cardiotonic effect of isoproterenol, an agonist of beta-adrenoceptors, without any increase in Emax, suggesting that a common mechanism was involved. Therefore, polyamines might modulate the cAMP production associated with the cardiotonic effect of androgens.
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Interaction of Androgens with Cardiotonic Drugs in Isolated Left Atrium of Rat
Pharmacology, 2004Co-Authors: Lorena Secades, Agustín Hidalgo, Lucía Velasco, Javier Bordallo, Rosario Cortina, Manuel SánchezAbstract:Pharmacological concentrations of androgens are known to elicit a rapid positive Inotropism in isolated left atrium of male rats. Upon short-term exposure to androgens, an increase in intracellular cA
Bruno Tota - One of the best experts on this subject based on the ideXlab platform.
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Cytoskeleton mediates negative Inotropism and lusitropism of chromogranin A-derived peptides (human vasostatin1-78 and rat CgA1-64) in the rat heart
Regulatory peptides, 2009Co-Authors: Tommaso Angelone, Bruno Tota, Angelo Corti, Rosa Mazza, Alfonsina Gattuso, A.m. Quintieri, Yannich Goumon, Valentina Di Felice, E. Filice, Marie-hélène Metz-boutigueAbstract:Abstract Cytoskeleton scaffold in cardiac myocytes provides structural support and compartmentalization of intracellular components. It is implicated in cardiac pathologies including hypertrophy and failure, playing a key role in the determinism of contractile and diastolic dysfunctions. Chromogranin A (CgA) and its derived peptides have revealed themselves as novel cardiovascular modulators. In humans, normal CgA levels considerably increase in several pathologies, including heart failure. Recent data have shown on the unstimulated rat heart that human recombinant Vasostatin-1 (hrVS-1) and rat chromogranin A 1-64 (rCgA1-64) induce negative inotropic and lusitropic effects counteracting the β-adrenergic-dependent positive Inotropism with a functional non-competitive antagonism. This study investigates, on the isolated Langendorff perfused rat heart, whether cardiac cytoskeleton is involved in the modulation of contractility and relaxation exerted by hrVS-1 and rCgA1-64. Cytoskeleton impairment by either cytochalasin-D (actin polymerization inhibitor), BDM (myosin ATP-ase antagonist) or wortmannin (inhibitor of PI3-K/Akt transduction cascade), or W-7 (calcium–calmodulin antagonist) abolished hrVS-1 and rCgA1-64-mediated Inotropism and lusitropism. Using fluorescent phalloidin, we showed on rat cardiac H9C2 cells that hrVS-1 (10 nM ÷ 10 µM) stimulates actin polymerization. Taken together these data indicate that in the rat heart, the actin cytoskeletal network strongly contributes to the cardiotropic action of CgA-derived peptides.
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Morphological and physiological study of the cardiac NOS/NO system in the Antarctic (Hb-/Mb-) icefish Chaenocephalus aceratus and in the red-blooded Trematomus bernacchii.
Nitric Oxide, 2009Co-Authors: Filippo Garofalo, Bruce D. Sidell, Bruno Tota, Daniela Amelio, Maria Carmela Cerra, Daniela PellegrinoAbstract:Abstract The nitric oxide synthase (NOS)/nitric oxide (NO) system integrates cellular biochemical machinery and energetics. In heart microenvironment, dynamic NO behaviour depends upon the presence of superoxide anions, haemoglobin (Hb), and myoglobin (Mb), being hemoproteins are major players disarming NO bioactivity. The Antarctic icefish, which lack Hb and, in some species, also cardiac Mb, represent a unique model for exploring Hb and Mb impact on NOS/NO function. We report in the (Hb−/Mb−) icefish Chaenocephalus aceratus the presence of cardiac NOSs activity (NADPH-diaphorase) and endothelial NOS (eNOS)/inducible NOS (iNOS) zonal immuno-localization in the myocardium. eNOS is localized on endocardium and, to a lesser extent, in myocardiocytes, while iNOS is localized exclusively in myocardiocytes. Confronting eNOS and iNOS expression in Trematomus bernacchii (Hb+/Mb+), C. hamatus (Hb−/Mb+) and C. aceratus (Hb−/Mb−) is evident a lower expression in the Mb-less icefish. NO signaling was analyzed using isolated working heart preparations. In T. bernacchii, l -arginine and exogenous (SIN-1) NO donor dose-dependently decreased stroke volume, indicating decreased Inotropism. l -arginine-induced Inotropism was NOSs-dependent, being abolished by NOSs-inhibitor NG-monomethyl- l -arginine ( l -NMMA). A SIN-1-induced negative Inotropism was found in presence of SOD. NOS inhibition by l -N5-N-iminoethyl- l -ornithine ( l -NIO) and l -NMMA confirmed the NO-mediated negative inotropic influence on cardiac performance. In contrast, in C. aceratus, l -arginine elicited a positive Inotropism. SIN-1 induced a negative Inotropism, which disappeared in presence of SOD, indicating peroxynitrite involvement. Cardiac performance was unaffected by l -NIO and l -NIL. NO signaling acted via a cGMP-independent mechanism. This high conservation degree of NOS localization pattern and signaling highlights its importance for cardiac biology.
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Recombinant N-terminal fragments of chromogranin-A modulate cardiac function of the Langendorff-perfused rat heart.
Basic research in cardiology, 2005Co-Authors: Maria Carmela Cerra, Tommaso Angelone, Angelo Corti, Lucia De Iuri, Bruno TotaAbstract:In this study we tested the hypothesis that vasostatins could act as myocardial modulators in the mammalian heart. Using the Langendorff–perfused rat heart, the cardiac effects of the two recombinant human CGA N–terminal fragments STA–CGA1–78 and STA–CGA1–115, containing the vasostatin–1 (CGA 1–76) and vasostatin–2 (CGA 1–113) sequences, respectively, were evaluated at concentrations of 11 ÷ 165 nM. Cardiac performance was evaluated by analyzing left ventricular pressure (LVP) and the rate pressure product (RPP: HR × LVP), used as indexes of contractile activity and cardiac work, respectively. Under basal conditions, STA–CGA1–78 at all concentrations tested elicited a dose–dependent negative Inotropism (LVP variations ranging from –9.6% ± 2 to –23% ± 2.9) without affecting coronary pressure (CP). In contrast, STA–CGA1–115 increased CP at 110 and 165 nM without affecting Inotropism. Both STA–CGA1–78 and STA–CGA1–115 counteracted the cardio–stimulatory effects of isoproterenol (ISO). The ISO–dependent positive chronotropism was unaffected by STA–CGA1–78, while being reduced by STA–CGA1–115. Both peptides abolished the ISO–induced positive Inotropism without modifying either the β–adrenergic–dependent coronary dilation or the ouabain–induced positive Inotropism. The analysis of the percentage of variations of RPP in terms of EC50 values of ISO alone (–8.5 ± 0.3; r2 = 0.88) and in presence of STA–CGA1–78 (11, or 33, or 65 nM: –7.7 ± 0.15, r2 = 0.97; –7.7 ± 0.15, r2 = 0.97; –7.8 ± 0.78, r2 = 0.55, respectively) revealed a non–competitive type of antagonism of STA–CGA1–78. Taken together, these data suggest vasostatins as novel cardioregulatory peptides in mammals.
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Influence of vasostatins, the chromogranin A-derived peptides, on the working heart of the eel (Anguilla anguilla): negative inotropy and mechanism of action.
General and comparative endocrinology, 2004Co-Authors: Sandra Imbrogno, Tommaso Angelone, Angelo Corti, C. Adamo, Karen B. Helle, Bruno TotaAbstract:We have studied the effects of exogenous human recombinant Vasostatin-1 (VS-1), Vasostatin-2 (VS-2) and the human Chromogranin A (CGA) 7-57 synthetic peptides on the mechanical performance of the isolated and perfused working eel (Anguilla anguilla) heart. Under basal conditions, the three peptides decreased stroke volume (SV) and stroke work (SW), thus exerting negative Inotropism. The VS-1-mediated negative Inotropism was abolished by exposure to inhibitors of either Gi/o protein (pertussis toxin; PTx) or M1 muscarinic receptors (Pirenzepine) or calcium (Lantanum and Diltiazem) and potassium (Ba2+, 4-aminopyridine, tetraethylammonium, glibenclamide) channels, while it required an intact endocardial endothelium (EE). Using NG-monomethyl-L-arginine (L-NMMA) as an inhibitor of nitric oxide (NO) synthase (NOS), and hemoglobin as a NO scavenger, we demonstrated the obligatory role of NO signaling in mediating the vasostatin response. Pretreatment with either a specific inhibitor of soluble guanylate cyclase (GC) 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ), or the inhibitor of the cGMP-activated protein kinase (PKG) KT5823, abolished the VS-1-mediated Inotropism, indicating the cGMP-PKG component as a crucial target of NO signaling. Of note, VS-1 was effective in counteracting the adrenergic (Isoproterenol and Phenylephrine)-mediated positive Inotropism. These findings provide the first evidence that vasostatins exert cardiotropic action in fish, thus suggesting their long evolutionary history as well as their species-specific mechanisms of action.
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Chromogranin A N-terminal fragments vasostatin-1 and the synthetic CGA 7-57 peptide act as cardiostatins on the isolated working frog heart.
General and comparative endocrinology, 2004Co-Authors: Angelo Corti, Tommaso Angelone, C. Mannarino, Rosa Mazza, Renato Longhi, Bruno TotaAbstract:Abstract Chromogranin A (CGA) N-terminal fragments corresponding to residues 1–76 and 1–113, named vasostatins for their inhibitory effects on vascular tension, have been postulated as important homeostatic regulators of the cardiovascular system. We have used an in vitro isolated working frog (Rana esculenta) heart as a bioassay to study the effects of exogenous human recombinant CGA 1–76 (VS-1) and human CGA 7–57 synthetic peptide on cardiac performance. Under basal conditions, the concentration–response curves of the two peptides exhibited a significant negative Inotropism. This vasostatin response was unaffected by pretreatment with either Triton X-100 or two nitric oxide synthase inhibitors, i.e., NG-monomethyl- l -arginine and l -N5(1-iminoethyl) ornithine or the soluble guanylate cyclase inhibitor 1H-(1,2,4) oxadiazolo-(4,3-a) quinoxalin-1-one, indicating an endocardial endothelium–nitric oxide–cGMP-independent mechanism. The negative Inotropism was also unaffected by either adrenergic (i.e., phentolamine and propranolol) or muscarinic (atropine) receptor or G proteins (pertussis toxin) inhibition. On the contrary, it was dependent from both extracellular Ca2+ and K+ channels, since it was abolished by pretreatment to either the Ca2+ channel inhibitors lanthanum and diltiazem or the K+ channel inhibitors Ba2+, 4-aminopyridine, tetraethylammonium chloride, and glibenclamide. In conclusion, the findings that vasostatins exert an inhibitory modulation on basal cardiac performance and counteract, as previously reported, the adrenergic-mediated positive Inotropism, strongly support a cardio-regulatory role for these peptides.
Suhn Hee Kim - One of the best experts on this subject based on the ideXlab platform.
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Different response of ANP secretion to adrenoceptor stimulation in renal hypertensive rat atria.
Peptides, 2008Co-Authors: Kuichang Yuan, Kyoung-suk Rhee, Woo Hyun Park, Soo Wan Kim, Suhn Hee KimAbstract:Sympathetic nervous system and atrial natriuretic peptide (ANP) system play fundamental roles in the regulation of cardiovascular functions. Overactivity of sympathetic nervous system can lead into cardiovascular diseases such as heart failure and hypertension. The present study aimed to define which adrenergic receptors (ARs) affect atrial contractility and ANP release and to determine their modification in renal hypertensive rat atria. An alpha(1)-AR agonist, cirazoline increased ANP release with positive Inotropism. These alpha(1)-AR agonist-mediated responses were attenuated by the alpha(1A)-AR antagonist, but not by the alpha(1B)- or alpha(1D)-AR antagonist. An alpha(2)-AR agonist, guanabenz and clonidine increased ANP release with negative Inotropism and decreased cAMP level. The order of potency for the increased ANP release was cirazoline>>phenylephrine=guanabenz>>clonidine. In contrast, a beta-AR agonist, isoproterenol decreased ANP release with positive Inotropism and these responses were blocked by the beta(1)-AR antagonist but not by the beta(2)-AR antagonist. The increased cAMP level by isoproterenol was suppressed by pretreatment with both beta(1)- and beta(2)-AR antagonists. In renal hypertensive rat atria, the effects of isoproterenol on atrial contractility, ANP release, and cAMP level were attenuated whereas the effect of cirazoline on ANP release was unaltered. Atrial beta(1)-AR mRNA level but not alpha(1A)-AR mRNA level was decreased in renal hypertensive rats. These findings suggest that alpha(1A)- and beta(1)-AR oppositely regulate atrial ANP release and that atrial beta(1)-AR expression/function is impaired in renal hypertensive rats.
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Adenosine-Stimulated Atrial Natriuretic Peptide Release Through A1 Receptor Subtype
Hypertension (Dallas Tex. : 1979), 2005Co-Authors: Kuichang Yuan, Chunhua Cao, Jeong Hee Han, Sung Zoo Kim, Suhn Hee KimAbstract:Adenosine acts as an important protector of ischemic myocardium through coronary vasodilation and the depression of cardiac contractility. The protective effect of adenosine may partly relate to the cardiac hormone atrial natriuretic peptide (ANP). The aim of the present study was to investigate the effects of adenosine and the adenosine receptor subtype on atrial hemodynamics and ANP release using isolated perfused beating rat atria. Adenosine, a nonselective adenosine receptor agonist, increased the ANP release with negative Inotropism in a dose-dependent manner. Adenosine-stimulated ANP release was attenuated by a selective A1 antagonist but not A(2A) antagonist or A3 antagonist. The order of potency of the various agonists for the ANP release was A1 agonists>>A3 agonist=adenosine>A(2A) agonist. The order of potency for the negative inotropy was A1 agonists>adenosine=A(2A) agonist>A3 agonist. The negative Inotropism and ANP release by a specific A1 agonist (N6-cyclopentyl-adenosine) were also attenuated by A1 antagonist but not A(2A) antagonist or A3 antagonist. Treatment with A1 agonist resulted in a decrease of cAMP contents in atria and perfusates. The agonist-stimulated ANP release was significantly attenuated in the presence of forskolin, isoproterenol 8-Br-cAMP, or an adenylyl cyclase inhibitor. These results suggest that the A1 receptor subtype is responsible for the adenosine-induced ANP release and negative Inotropism through adenylyl cyclase-cAMP pathway.
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ATP-stimulated ANP release through P1 receptor subtype.
Regulatory peptides, 2005Co-Authors: Chunhua Cao, Feng Lian Piao, Jeong Hee Han, Sung Zoo Kim, Suhn Hee KimAbstract:Extracellular ATP acts as a local regulator of physiological functions in the cardiovascular system via P1 and P2 receptors. However, little is known about the effect of ATP on the release of atrial natriuretic peptide (ANP) secretion. The purpose of this study was to investigate the effects of extracellular ATP on atrial hemodynamics and ANP release and to identify their receptor-mediated mechanism. ATP was infused into isolated perfused beating rat atria in the absence and presence of various receptor antagonists. ATP (from 0.1 to 30 microM) increased the ANP release with negative Inotropism in a dose-dependent manner. ADP (30 microM) also caused an increase in ANP release with similarity to ATP, but alpha,beta-methylene ATP (alpha,beta-MeATP, P2X1 receptor agonist) and 2-methylthioADP (2-MesADP, P2Y1 receptor agonist) did not. The rank order of potency for the increment of ANP release was adenosine>ATP=ADP>2-MesADP>alpha,beta-MeATP. In contrast, UTP, an agonist for P2Y2,4,6 receptor, caused a decrease in ANP release without changes in contractility. Extracellular ATP-induced increase in ANP release and negative Inotropism were completely blocked by the pretreatment of 8-cyclopentyl-1,3-dipropylxanthine (P1 receptor antagonist), but not by pyridoxal phosphate-6-azobenzene-2,4-disulfonic acid (P2X1 receptor antagonist) and suramin (P2XY receptor antagonist). Reactive Blue 2 (P2Y receptor antagonist) caused an augmentation of ATP-induced increase in ANP release without affecting negative Inotropism. Adenosine 5'-(alpha,beta-methylene) diphosphate, an ectonucleotidase inhibitor, did not affect ATP-induced augmentation of ANP release with negative inotropy. These results suggest that extracellular ATP-induced increase in ANP release and negative Inotropism are mediated mainly by P1 receptor, and UTP decreases ANP release. Therefore, we suggest that extracellular ATP and UTP may have opposite actions on the regulation of ANP secretion.
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ATP-stimulated ANP release through P1 receptor subtype.
Regulatory Peptides, 2004Co-Authors: Chunhua Cao, Feng Lian Piao, Jeong Hee Han, Sung Zoo Kim, Suhn Hee KimAbstract:Abstract Extracellular ATP acts as a local regulator of physiological functions in the cardiovascular system via P1 and P2 receptors. However, little is known about the effect of ATP on the release of atrial natriuretic peptide (ANP) secretion. The purpose of this study was to investigate the effects of extracellular ATP on atrial hemodynamics and ANP release and to identify their receptor-mediated mechanism. ATP was infused into isolated perfused beating rat atria in the absence and presence of various receptor antagonists. ATP (from 0.1 to 30 μM) increased the ANP release with negative Inotropism in a dose-dependent manner. ADP (30 μM ) also caused an increase in ANP release with similarity to ATP, but α,β-methylene ATP (α,β-MeATP, P2X1 receptor agonist) and 2-methylthioADP (2-MesADP, P2Y1 receptor agonist) did not. The rank order of potency for the increment of ANP release was adenosine>ATP=ADP>2-MesADP>α,β-MeATP. In contrast, UTP, an agonist for P2Y2,4,6 receptor, caused a decrease in ANP release without changes in contractility. Extracellular ATP-induced increase in ANP release and negative Inotropism were completely blocked by the pretreatment of 8-cyclopentyl-1,3-dipropylxanthine (P1 receptor antagonist), but not by pyridoxal phosphate-6-azobenzene-2,4-disulfonic acid (P2X1 receptor antagonist) and suramin (P2XY receptor antagonist). Reactive Blue 2 (P2Y receptor antagonist) caused an augmentation of ATP-induced increase in ANP release without affecting negative Inotropism. Adenosine 5′-(α,β-methylene) diphosphate, an ectonucleotidase inhibitor, did not affect ATP-induced augmentation of ANP release with negative inotropy. These results suggest that extracellular ATP-induced increase in ANP release and negative Inotropism are mediated mainly by P1 receptor, and UTP decreases ANP release. Therefore, we suggest that extracellular ATP and UTP may have opposite actions on the regulation of ANP secretion.
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Calcitonin gene-related peptide-induced suppression of atrial natriuretic peptide release through receptors for CGRP1 but not for calcitonin and amylin.
European journal of pharmacology, 2004Co-Authors: Feng Lian Piao, Chunhua Cao, Jeong Hee Han, Sung Zoo Kim, Suhn Hee KimAbstract:Calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide, is found in the central nervous system as well as in the heart. CGRP shows high sequence homology with amylin, salmon calcitonin, and adrenomedullin. This study aimed to investigate the effect of CGRP on atrial hemodynamics and atrial natriuretic peptide (ANP) release by using isolated perfused beating left atria and to identify its receptor subtypes. Rat alpha-CGRP (0.1, 1, 10, or 100 nM) increased atrial contractility and suppressed the release of ANP in a concentration-dependent manner. However, cys-CGRP (1 microM), a CGRP(2) receptor agonist, slightly decreased ANP release without positive Inotropism. Human alpha-CGRP (1 nM) showed an effect on ANP release similar to that of rat alpha-CGRP with potent positive Inotropism. However, salmon and rat calcitonin (1 microM) caused a slight decrease or no change in ANP release. Pretreatment with a receptor antagonist for CGRP(1) [rat alpha-CGRP-(8-37)] blocked rat alpha-CGRP-induced suppression of ANP release and positive Inotropism, whereas the antagonists for salmon or amylin did not. Therefore, we suggest that rat alpha-CGRP causes a suppression of ANP release with positive Inotropism through the receptor for CGRP(1) but not that for calcitonin and amylin.
Laura Caparrotta - One of the best experts on this subject based on the ideXlab platform.
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Are prostanoids related to positive Inotropism by UTP and ATP
Pharmacology, 2004Co-Authors: Guglielmina Froldi, Giampietro Galzignato, Miriam Zanetti, Monica Montopoli, Paola Dorigo, Laura CaparrottaAbstract:Uridine 5'-triphosphate (UTP) and adenosine 5'-triphosphate (ATP) induce biphasic inotropic effects: first a decrease and then an increase in contractile tension were observed in isolated rat myocardial tissues. Inotropic effects were higher in atrial tissue than in ventricular or papillary muscle; thus, experiments were mostly carried out on rat atria. In this research, we mainly studied positive Inotropism by using selective inhibitors of the arachidonic acid cascade. The natural compounds luffariellolide and aristolochic acid, two inhibitors of PLA2, both inhibited positive Inotropism by UTP but not by ATP, whereas they did not modify their negative Inotropism. Indomethacin (5 micromol/l), an inhibitor of COX-1, reduced positive Inotropism by UTP but not by ATP, without modifying their negative Inotropism. Nimesulide (1 micromol/l), an inhibitor of COX-2, did not change any of the effects caused by nucleotides. Nor did NDGA (10 micromol/l), an inhibitor of lipoxygenase, change Inotropism by nucleotides. Arachidonic acid pretreatment (10 micromol/l) increased inotropic effects by UTP without affecting those of ATP. These data suggest that there are differences in the mechanisms responsible for the positive Inotropism caused by UTP in comparison with ATP; the effect of UTP depends on PLA2 activation and PG(s) release, whereas that of ATP does not.
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do atp and utp involve cgmp in positive Inotropism on rat atria
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2001Co-Authors: Guglielmina Froldi, Eugenio Ragazzi, Laura CaparrottaAbstract:Abstract ATP and UTP induced a dual inotropic effect in rat left atria: first a decrease and then an increase in contractile tension were observed. PPADS, an antagonist of P2X receptors, inhibited positive Inotropism induced by ATP and α,β-meATP. Chiefly, we investigated intracellular mechanisms responsible for the positive Inotropism. We tested cromakalim and glibenclamide, an activator and an inhibitor, respectively, of ATP-sensitive K + channels. These compounds did not influence the effects of ATP. IBMX, a phosphodiesterase inhibitor, and H-7, an inhibitor of protein kinase C and cAMP-dependent protein kinase, did not modify the inotropic effects of ATP. Instead, H-8, an inhibitor of cAMP- and cGMP-dependent protein kinases, strongly inhibited the positive effects of both ATP and UTP, suggesting the possible involvement of cGMP in the Inotropism. Also, LY 83583, an inhibitor of cGMP production, reduced positive Inotropism by α,β-meATP, ATP and UTP. Moreover, 8-Br-cGMP (50 μM), a stable analogue of cGMP, inhibited positive Inotropism by all nucleotides. Lastly, we determined intracellular cGMP levels by RIA; the cyclic nucleotide increased during positive Inotropism induced by ATP and UTP. The results regarding positive Inotropism suggest that: (a) ATP acts through P2X receptors, while UTP may act by P2X, but also through PPADS-insensitive receptors; and (b) changes in intracellular cGMP concentration are involved in this inotropic effect.
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Do ATP and UTP involve cGMP in positive Inotropism on rat atria
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 2001Co-Authors: Guglielmina Froldi, Eugenio Ragazzi, Laura CaparrottaAbstract:ATP and UTP induced a dual inotropic effect in rat left atria: first a decrease and then an increase in contractile tension were observed. PPADS, an antagonist of P2X receptors, inhibited positive Inotropism induced by ATP and alpha,beta-meATP. Chiefly, we investigated intracellular mechanisms responsible for the positive Inotropism. We tested cromakalim and glibenclamide, an activator and an inhibitor, respectively, of ATP-sensitive K(+) channels. These compounds did not influence the effects of ATP. IBMX, a phosphodiesterase inhibitor, and H-7, an inhibitor of protein kinase C and cAMP-dependent protein kinase, did not modify the inotropic effects of ATP. Instead, H-8, an inhibitor of cAMP- and cGMP-dependent protein kinases, strongly inhibited the positive effects of both ATP and UTP, suggesting the possible involvement of cGMP in the Inotropism. Also, LY 83583, an inhibitor of cGMP production, reduced positive Inotropism by alpha,beta-meATP, ATP and UTP. Moreover, 8-Br-cGMP (50 microM), a stable analogue of cGMP, inhibited positive Inotropism by all nucleotides. Lastly, we determined intracellular cGMP levels by RIA; the cyclic nucleotide increased during positive Inotropism induced by ATP and UTP. The results regarding positive Inotropism suggest that: (a) ATP acts through P2X receptors, while UTP may act by P2X, but also through PPADS-insensitive receptors; and (b) changes in intracellular cGMP concentration are involved in this inotropic effect.
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6-Benzylaminopurine: A Plant Derived Cytokinin Inducing Positive Inotropism by P2-Purinoceptors
Planta medica, 1999Co-Authors: Guglielmina Froldi, Eugenio Ragazzi, U Gallo, Laura CaparrottaAbstract:Positive inotropic effects induced by 6-benzylaminopurine (6-BAP), kinetin and zeatin were studied in rat atria. The potency order observed was 6-BAP > or = kinetin > zeatin. Suramin, a P2-purinoceptor antagonist, inhibited the positive effect of 6-BAP suggesting the involvement of P2-purinoceptors in the positive effect of this cytokinin. In order to elucidate this point, 6-BAP was used against R-PIA (a P1-purinoceptor agonist) and ATP and UTP (both P2-purinoceptor agonists). 6-BAP did not influence negative Inotropism by R-PIA whereas both nucleotides were inhibited after pretreatment with the cytokinin. LY 83583, an inhibitor of cGMP production, reduced the inotropic effect by cytokinin whereas L-NAME, an inhibitor of the L-arginine/nitric oxide pathway, did not influence the effect induced by 6-BAP. Indomethacin, an inhibitor of cyclooxygenase, and neomycin, an inhibitor of phospholipase C, did not significantly modify positive Inotropism by 6-BAP. Verapamil, an inhibitor of L-type calcium channels, did not change the positive effect of 6-BAP while TMB-8 and dantrolene, two inhibitors of intracellular calcium release, reduced the increase of contractile tension induced by cytokinin. Our data on rat atria suggest that 6-BAP causes a positive Inotropism through activation of P2-purinoceptors, involving modification of cGMP and of intracellular calcium.
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Dual effect of ATP and UTP on rat atria: which types of receptors are involved?
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994Co-Authors: Guglielmina Froldi, Andrea Chinellato, Laura Caparrotta, Luciano Pandolfo, Eugenio Ragazzi, Giorgio FassinaAbstract:The effects of adenine compounds and UTP were examined in electrically driven rat left atria. ATP, ADP, AMP, adenosine and UTP caused a dual inotropic effect: first a rapid decrease in contractility, and second an increase in contractile tension. alpha,beta-Methylene ATP caused an increase in contractile tension only, whereas 2-methylthio-ATP only induced a negative inotropic effect, 1,3-Dipropyl-8-cyclopentylxanthine inhibited the negative effects of ATP and adenosine, whereas 3,7-dimethyl-1-propargylxanthine did not influence the effects of ATP. Suramin but not reactive blue 2 antagonized the positive Inotropism induced by ATP and alpha,beta-methylene ATP. Suramin also abolished the positive inotropic effect induced by UTP. These results demonstrate that ATP may induce negative Inotropism directly by an action on A1-adenosine receptors and positive Inotropism by an action on P2x-purinoceptors. UTP induces a positive inotropic effect mediated by suramin-sensitive receptors.
Guglielmina Froldi - One of the best experts on this subject based on the ideXlab platform.
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Are prostanoids related to positive Inotropism by UTP and ATP
Pharmacology, 2004Co-Authors: Guglielmina Froldi, Giampietro Galzignato, Miriam Zanetti, Monica Montopoli, Paola Dorigo, Laura CaparrottaAbstract:Uridine 5'-triphosphate (UTP) and adenosine 5'-triphosphate (ATP) induce biphasic inotropic effects: first a decrease and then an increase in contractile tension were observed in isolated rat myocardial tissues. Inotropic effects were higher in atrial tissue than in ventricular or papillary muscle; thus, experiments were mostly carried out on rat atria. In this research, we mainly studied positive Inotropism by using selective inhibitors of the arachidonic acid cascade. The natural compounds luffariellolide and aristolochic acid, two inhibitors of PLA2, both inhibited positive Inotropism by UTP but not by ATP, whereas they did not modify their negative Inotropism. Indomethacin (5 micromol/l), an inhibitor of COX-1, reduced positive Inotropism by UTP but not by ATP, without modifying their negative Inotropism. Nimesulide (1 micromol/l), an inhibitor of COX-2, did not change any of the effects caused by nucleotides. Nor did NDGA (10 micromol/l), an inhibitor of lipoxygenase, change Inotropism by nucleotides. Arachidonic acid pretreatment (10 micromol/l) increased inotropic effects by UTP without affecting those of ATP. These data suggest that there are differences in the mechanisms responsible for the positive Inotropism caused by UTP in comparison with ATP; the effect of UTP depends on PLA2 activation and PG(s) release, whereas that of ATP does not.
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do atp and utp involve cgmp in positive Inotropism on rat atria
Comparative Biochemistry and Physiology C-toxicology & Pharmacology, 2001Co-Authors: Guglielmina Froldi, Eugenio Ragazzi, Laura CaparrottaAbstract:Abstract ATP and UTP induced a dual inotropic effect in rat left atria: first a decrease and then an increase in contractile tension were observed. PPADS, an antagonist of P2X receptors, inhibited positive Inotropism induced by ATP and α,β-meATP. Chiefly, we investigated intracellular mechanisms responsible for the positive Inotropism. We tested cromakalim and glibenclamide, an activator and an inhibitor, respectively, of ATP-sensitive K + channels. These compounds did not influence the effects of ATP. IBMX, a phosphodiesterase inhibitor, and H-7, an inhibitor of protein kinase C and cAMP-dependent protein kinase, did not modify the inotropic effects of ATP. Instead, H-8, an inhibitor of cAMP- and cGMP-dependent protein kinases, strongly inhibited the positive effects of both ATP and UTP, suggesting the possible involvement of cGMP in the Inotropism. Also, LY 83583, an inhibitor of cGMP production, reduced positive Inotropism by α,β-meATP, ATP and UTP. Moreover, 8-Br-cGMP (50 μM), a stable analogue of cGMP, inhibited positive Inotropism by all nucleotides. Lastly, we determined intracellular cGMP levels by RIA; the cyclic nucleotide increased during positive Inotropism induced by ATP and UTP. The results regarding positive Inotropism suggest that: (a) ATP acts through P2X receptors, while UTP may act by P2X, but also through PPADS-insensitive receptors; and (b) changes in intracellular cGMP concentration are involved in this inotropic effect.
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Do ATP and UTP involve cGMP in positive Inotropism on rat atria
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 2001Co-Authors: Guglielmina Froldi, Eugenio Ragazzi, Laura CaparrottaAbstract:ATP and UTP induced a dual inotropic effect in rat left atria: first a decrease and then an increase in contractile tension were observed. PPADS, an antagonist of P2X receptors, inhibited positive Inotropism induced by ATP and alpha,beta-meATP. Chiefly, we investigated intracellular mechanisms responsible for the positive Inotropism. We tested cromakalim and glibenclamide, an activator and an inhibitor, respectively, of ATP-sensitive K(+) channels. These compounds did not influence the effects of ATP. IBMX, a phosphodiesterase inhibitor, and H-7, an inhibitor of protein kinase C and cAMP-dependent protein kinase, did not modify the inotropic effects of ATP. Instead, H-8, an inhibitor of cAMP- and cGMP-dependent protein kinases, strongly inhibited the positive effects of both ATP and UTP, suggesting the possible involvement of cGMP in the Inotropism. Also, LY 83583, an inhibitor of cGMP production, reduced positive Inotropism by alpha,beta-meATP, ATP and UTP. Moreover, 8-Br-cGMP (50 microM), a stable analogue of cGMP, inhibited positive Inotropism by all nucleotides. Lastly, we determined intracellular cGMP levels by RIA; the cyclic nucleotide increased during positive Inotropism induced by ATP and UTP. The results regarding positive Inotropism suggest that: (a) ATP acts through P2X receptors, while UTP may act by P2X, but also through PPADS-insensitive receptors; and (b) changes in intracellular cGMP concentration are involved in this inotropic effect.
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6-Benzylaminopurine: A Plant Derived Cytokinin Inducing Positive Inotropism by P2-Purinoceptors
Planta medica, 1999Co-Authors: Guglielmina Froldi, Eugenio Ragazzi, U Gallo, Laura CaparrottaAbstract:Positive inotropic effects induced by 6-benzylaminopurine (6-BAP), kinetin and zeatin were studied in rat atria. The potency order observed was 6-BAP > or = kinetin > zeatin. Suramin, a P2-purinoceptor antagonist, inhibited the positive effect of 6-BAP suggesting the involvement of P2-purinoceptors in the positive effect of this cytokinin. In order to elucidate this point, 6-BAP was used against R-PIA (a P1-purinoceptor agonist) and ATP and UTP (both P2-purinoceptor agonists). 6-BAP did not influence negative Inotropism by R-PIA whereas both nucleotides were inhibited after pretreatment with the cytokinin. LY 83583, an inhibitor of cGMP production, reduced the inotropic effect by cytokinin whereas L-NAME, an inhibitor of the L-arginine/nitric oxide pathway, did not influence the effect induced by 6-BAP. Indomethacin, an inhibitor of cyclooxygenase, and neomycin, an inhibitor of phospholipase C, did not significantly modify positive Inotropism by 6-BAP. Verapamil, an inhibitor of L-type calcium channels, did not change the positive effect of 6-BAP while TMB-8 and dantrolene, two inhibitors of intracellular calcium release, reduced the increase of contractile tension induced by cytokinin. Our data on rat atria suggest that 6-BAP causes a positive Inotropism through activation of P2-purinoceptors, involving modification of cGMP and of intracellular calcium.
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Dual effect of ATP and UTP on rat atria: which types of receptors are involved?
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994Co-Authors: Guglielmina Froldi, Andrea Chinellato, Laura Caparrotta, Luciano Pandolfo, Eugenio Ragazzi, Giorgio FassinaAbstract:The effects of adenine compounds and UTP were examined in electrically driven rat left atria. ATP, ADP, AMP, adenosine and UTP caused a dual inotropic effect: first a rapid decrease in contractility, and second an increase in contractile tension. alpha,beta-Methylene ATP caused an increase in contractile tension only, whereas 2-methylthio-ATP only induced a negative inotropic effect, 1,3-Dipropyl-8-cyclopentylxanthine inhibited the negative effects of ATP and adenosine, whereas 3,7-dimethyl-1-propargylxanthine did not influence the effects of ATP. Suramin but not reactive blue 2 antagonized the positive Inotropism induced by ATP and alpha,beta-methylene ATP. Suramin also abolished the positive inotropic effect induced by UTP. These results demonstrate that ATP may induce negative Inotropism directly by an action on A1-adenosine receptors and positive Inotropism by an action on P2x-purinoceptors. UTP induces a positive inotropic effect mediated by suramin-sensitive receptors.