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Francisco M. Pinto - One of the best experts on this subject based on the ideXlab platform.
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Smooth muscle neurokinin-2 receptors mediate contraction in human saphenous veins
Pharmacological Research, 2011Co-Authors: Hakima Mechiche, Stanislas Grassin-delyle, Francisco M. Pinto, Amparo Buenestado, Luz Candenas, Philippe DevillierAbstract:Substance P (SP) and neurokinin A (NKA) are members of the Tachykinin peptides family. SP causes endothelial-dependant relaxation but the contractile response to Tachykinins in human vessels remains unknown. The objective was to assess the expression and the contractile effects of Tachykinins and their receptors in human saphenous veins (SV). Tachykinin expression was assessed with RT-PCR, Tachykinin receptors expression with RT-PCR and immunohistochemistry, and functional studies were performed in organ bath. Transcripts of all Tachykinin and Tachykinin receptor genes were found in SV. NK(1)-receptors were localized in both endothelial and smooth muscle layers of undistended SV, whereas they were only found in smooth muscle layers of varicose SV. The expression of NK(2)- and NK(3)-receptors was limited to the smooth muscle in both preparations. NKA induced concentration-dependent contractions in about half the varicose SV. Maximum effect reached 27.6±5.5% of 90 mM KCl and the pD(2) value was 7.3±0.2. NKA also induced the contraction of undistended veins from bypass and did not cause the relaxation of these vessels after precontraction. The NK(2)-receptor antagonist SR48968 abolished the contraction induced by NKA, and a rapid desensitization of the NK(2)-receptor was observed. In varicose SV, the agonists specific to NK(1)- or NK(3)-receptors did not cause either contraction or relaxation. The stimulation of smooth muscle NK(2)-receptors can induce the contraction of human SV. As SV is richly innervated, Tachykinins may participate in the regulation of the tone in this portion of the low pressure vascular system.
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Autocrine regulation of human sperm motility by Tachykinins.
Reproductive biology and endocrinology : RB&E, 2010Co-Authors: Francisco M. Pinto, Cristina G Ravina, Manuel Fernández-sánchez, Nerea Subirán, Antonio Cejudo-román, Jon Irazusta, Nicolas Garrido, Luz CandenasAbstract:Background: We examined the presence and function of Tachykinins and the Tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human spermatozoa. Methods: Freshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reversetranscriptase polymerase chain reaction (RT-PCR), western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of Tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computerassisted sperm analysis (CASA). Results: The mRNAs of the genes that encode substance P/neurokinin A (TAC1), neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2 (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that Tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the Tachykinin receptor antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor-selective) but unmodified in the presence of SR142801 (NK3 receptor-selective). Conclusion: These data show that Tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins.
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Ovarian steroids regulate Tachykinin and Tachykinin receptor gene expression in the mouse uterus
Reproductive biology and endocrinology : RB&E, 2009Co-Authors: Francisco M. Pinto, Jocelyn N Pennefather, Eva N Patak, C. Oscar Pintado, Luz CandenasAbstract:Background: In the mouse uterus, pregnancy is accompanied by changes in Tachykinin and Tachykinin receptor gene expression and in the uterotonic effects of endogenous Tachykinins. In this study we have investigated whether changes in Tachykinin expression and responses are a result of changes in ovarian steroid levels. Methods: We quantified the mRNAs of Tachykinins and Tachykinin receptors in uteri from ovariectomized mice and studied their regulation in response to estrogen and progesterone using real-time quantitative RT-PCR. Early (3 h) and late (24 h) responses to estrogen were evaluated and the participation of the estrogen receptors (ER), ERalpha and ERbeta, was analyzed by treating mice with propylpyrazole triol, a selective ERalpha agonist, or diarylpropionitrile, a selective agonist of ERbeta. Results: All genes encoding Tachykinins (Tac1, Tac2 and Tac4) and Tachykinin receptors (Tacr1, Tacr2 and Tacr3) were expressed in uteri from ovariectomized mice. Estrogen increased Tac1 and Tacr1 mRNA after 3 h and decreased Tac1 and Tac4 expression after 24 h. Tac2 and Tacr3 mRNA levels were decreased by estrogen at both 3 and 24 h. Most effects of estrogen were also observed in animals treated with propylpyrazole triol. Progesterone treatment increased the levels of Tac2. Conclusion: These results show that the expression of Tachykinins and their receptors in the mouse uterus is tightly and differentially regulated by ovarian steroids. Estrogen effects are mainly mediated by ERalpha supporting an essential role for this estrogen receptor in the regulation of the tachykinergic system in the mouse uterus.
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A role for Tachykinins in the regulation of human sperm motility
Human reproduction (Oxford England), 2007Co-Authors: Cristina G Ravina, Francisco M. Pinto, M. Seda, A. Orea, Manuel Fernández-sánchez, C.o. Pintado, M. Luz CandenasAbstract:BACKGROUND: Tachykinins and Tachykinin receptors are widely distributed in the male reproductive tract and appear to be involved in reproduction. However, the function and expression of Tachykinins and their receptors in human spermatozoa remain poorly studied. We analysed the effects of Tachykinins on sperm motility and characterized the population of Tachykinin receptors in human spermatozoa. METHODS AND RESULTS: Motility analysis was performed following World Health Organization guidelines and we found that substance P (SP), human hemokinin-1 (hHK-1), neurokinin A (NKA) and neurokinin B (NKB) produced concentration-dependent increases in sperm progressive motility. The effects of Tachykinins were antagonized by the NK 1 receptor-selective antagonist SR 140333, the NK 2 receptor-selective antagonist, SR 48968 and, to a lesser extent, also by the NK 3 receptor-selective antagonist SR 142801. Immunocytochemistry studies showed expression of the NK 1 , NK 2 and NK 3 Tachykinin receptor proteins in spermatozoa with different major sites of localization for each receptor. Western blot analysis confirmed the presence of Tachykinin receptors in sperm cell homogenates. RT-PCR demonstrated expression of the genes that encode SP/NKA (TACT), NKB (TAC3) and hHK-1 (TAC4) but not the genes TACR1, TACR2 and TACR3 encoding NK 1 , NK 2 and NK 3 receptors, respectively. CONCLUSIONS: These results show for the first time that the NK 1 , NK 2 and NK 3 Tachykinin receptor proteins are present in human spermatozoa. Our findings suggest that Tachykinins, probably acting through these three Tachykinin receptors, play a role in the regulation of human sperm motility.
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Functional and Molecular Characterization of Tachykinins and Tachykinin Receptors in the Mouse Uterus
Biology of reproduction, 2005Co-Authors: Eva N Patak, Nigel Page, Francisco M. Pinto, Jocelyn N Pennefather, Margot E Story, C. Oscar Pintado, Anna J Fleming, M. Luz CandenasAbstract:The aim of this study was to analyze the function and expression of Tachykinins, Tachykinin receptors, and neprilysin (NEP) in the mouse uterus. A previous study showed that the uterotonic effects of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) in estrogen-treated mice were mainly mediated by the Tachykinin NK1 receptor. In the present work, further contractility studies were undertaken to determine the nature of the receptors mediating responses to Tachykinins in uteri of late pregnant mice. Endpoint and real-time quantitative RT-PCR were used to analyze the expression of the genes that encode the Tachykinins SP/NKA, NKB, and hemokinin-1 (HK-1) (Tac1, Tac2, and Tac4); and the genes that encode Tachykinin NK1 (Tacr1), NK2 (Tacr2), and NK3 (Tacr3) receptors in uteri from pregnant and nonpregnant mice. The data show that the mRNAs of Tachykinins (particularly NKB and HK-1), Tachykinin receptors, and NEP are locally expressed in the mouse uterus, and their expression changes during the estrous cycle and during pregnancy. The Tachykinin NK1 receptor is the predominant Tachykinin receptor in the nonpregnant and early pregnant mouse and may mediate Tachykinin-induced uterine contractions in the nonpregnant mouse. The Tachykinin NK2 receptor is predominant in the late pregnant mouse and is the main receptor mediating uterotonic responses to Tachykinins at late pregnancy. The Tachykinin NK3 receptor is expressed in considerable amounts only in uteri from nonpregnant diestrous animals, and its physiological significance remains to be clarified.
M. Luz Candenas - One of the best experts on this subject based on the ideXlab platform.
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A role for Tachykinins in the regulation of human sperm motility
Human reproduction (Oxford England), 2007Co-Authors: Cristina G Ravina, Francisco M. Pinto, M. Seda, A. Orea, Manuel Fernández-sánchez, C.o. Pintado, M. Luz CandenasAbstract:BACKGROUND: Tachykinins and Tachykinin receptors are widely distributed in the male reproductive tract and appear to be involved in reproduction. However, the function and expression of Tachykinins and their receptors in human spermatozoa remain poorly studied. We analysed the effects of Tachykinins on sperm motility and characterized the population of Tachykinin receptors in human spermatozoa. METHODS AND RESULTS: Motility analysis was performed following World Health Organization guidelines and we found that substance P (SP), human hemokinin-1 (hHK-1), neurokinin A (NKA) and neurokinin B (NKB) produced concentration-dependent increases in sperm progressive motility. The effects of Tachykinins were antagonized by the NK 1 receptor-selective antagonist SR 140333, the NK 2 receptor-selective antagonist, SR 48968 and, to a lesser extent, also by the NK 3 receptor-selective antagonist SR 142801. Immunocytochemistry studies showed expression of the NK 1 , NK 2 and NK 3 Tachykinin receptor proteins in spermatozoa with different major sites of localization for each receptor. Western blot analysis confirmed the presence of Tachykinin receptors in sperm cell homogenates. RT-PCR demonstrated expression of the genes that encode SP/NKA (TACT), NKB (TAC3) and hHK-1 (TAC4) but not the genes TACR1, TACR2 and TACR3 encoding NK 1 , NK 2 and NK 3 receptors, respectively. CONCLUSIONS: These results show for the first time that the NK 1 , NK 2 and NK 3 Tachykinin receptor proteins are present in human spermatozoa. Our findings suggest that Tachykinins, probably acting through these three Tachykinin receptors, play a role in the regulation of human sperm motility.
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Functional and Molecular Characterization of Tachykinins and Tachykinin Receptors in the Mouse Uterus
Biology of reproduction, 2005Co-Authors: Eva N Patak, Nigel Page, Francisco M. Pinto, Jocelyn N Pennefather, Margot E Story, C. Oscar Pintado, Anna J Fleming, M. Luz CandenasAbstract:The aim of this study was to analyze the function and expression of Tachykinins, Tachykinin receptors, and neprilysin (NEP) in the mouse uterus. A previous study showed that the uterotonic effects of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) in estrogen-treated mice were mainly mediated by the Tachykinin NK1 receptor. In the present work, further contractility studies were undertaken to determine the nature of the receptors mediating responses to Tachykinins in uteri of late pregnant mice. Endpoint and real-time quantitative RT-PCR were used to analyze the expression of the genes that encode the Tachykinins SP/NKA, NKB, and hemokinin-1 (HK-1) (Tac1, Tac2, and Tac4); and the genes that encode Tachykinin NK1 (Tacr1), NK2 (Tacr2), and NK3 (Tacr3) receptors in uteri from pregnant and nonpregnant mice. The data show that the mRNAs of Tachykinins (particularly NKB and HK-1), Tachykinin receptors, and NEP are locally expressed in the mouse uterus, and their expression changes during the estrous cycle and during pregnancy. The Tachykinin NK1 receptor is the predominant Tachykinin receptor in the nonpregnant and early pregnant mouse and may mediate Tachykinin-induced uterine contractions in the nonpregnant mouse. The Tachykinin NK2 receptor is predominant in the late pregnant mouse and is the main receptor mediating uterotonic responses to Tachykinins at late pregnancy. The Tachykinin NK3 receptor is expressed in considerable amounts only in uteri from nonpregnant diestrous animals, and its physiological significance remains to be clarified.
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Mammalian Tachykinins and uterine smooth muscle: the challenge escalates
European Journal of Pharmacology, 2004Co-Authors: Jocelyn N Pennefather, Francisco M. Pinto, Eva N Patak, M. Luz CandenasAbstract:Abstract We review the actions of mammalian Tachykinins on uterine smooth muscle. Derived from sensory neurones and non-neuronal cells within the female reproductive tract, Tachykinins are potent uterotonic agents. Three Tachykinin receptor genes, and the gene encoding neprilysin, the enzyme that inactivates Tachykinins, are present in rat, mouse and human myometrium. In rat and human, the Tachykinin NK2 receptor is important in mediating the uterotonic effects of Tachykinins; actions at this receptor remain relatively stable or vary only slightly in the face of changing hormonal and gestational status. In contrast, ovarian steroids and pregnancy regulate expression of the Tachykinin NK3, and to a lesser extent, the Tachykinin NK1 receptor, as well as the activity of neprilysin. In the oestrogen primed mouse uterus, the Tachykinin NK1 receptor primarily mediates Tachykinin uterotonic effects, but there is a switch to the Tachykinin NK2 receptor by late pregnancy. The possible physiological and pathological roles of Tachykinins, including hemokinins and endokinins, in normal and premature labour, stress-induced abortion and menstrual disorders are briefly discussed.
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mRNA expression of Tachykinins and Tachykinin receptors in different human tissues.
European journal of pharmacology, 2004Co-Authors: Francisco M. Pinto, Philippe Devillier, Teresa A. Almeida, Mariano Hernández, Charles Advenier, M. Luz CandenasAbstract:The Tachykinins substance P, neurokinin A and neurokinin B are involved in many pathophysiological processes. A reverse transcription-polymerase chain reaction (RT-PCR) assay was used to analyse the expression of TAC1 and TAC3, the genes that encode substance P/neurokinin A and neurokinin B, respectively, and the genes encoding the Tachykinin NK(1), NK(2) and NK(3) receptors in different human tissues. The data show that Tachykinins and their receptors mRNAs are broadly distributed in different human tissues being present in neuronal and non-neuronal types of cells. The presence of TAC3 and the Tachykinin NK(3) receptor (TACR3) in a wide variety of peripheral tissues argue for a still unexplored role of this ligand-receptor pair in mediating visceral effects of Tachykinins. We found, for the first time, that TAC3 and TACR3 mRNAs are expressed in human airways and pulmonary arteries and veins, providing further evidence for the involvement of this system in lung physiopathology.
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Tachykinins and Tachykinin receptors: a growing family
Life sciences, 2004Co-Authors: Jocelyn N Pennefather, Alessandro Lecci, Francisco M. Pinto, Eva N Patak, M. Luz Candenas, Carlo Alberti MaggiAbstract:The peptides of the Tachykinin family are widely distributed within the mammalian peripheral and central nervous systems and play a well-recognized role as excitatory neurotransmitters. Currently, the concept that Tachykinins act exclusively as neuropeptides is being challenged, since the best known members of the family, substance P, neurokinin A and neurokinin B, are also present in non-neuronal cells and in non-innervated tissues. Moreover, the recently cloned mammalian Tachykinins hemokinin-1 and endokinins are primarily expressed in non-neuronal cells, suggesting a widespread distribution and important role for these peptides as intercellular signaling molecules. The biological actions of Tachykinins are mediated through three types of receptors denoted NK 1 , NK 2 and NK 3 that belong to the family of G protein-coupled receptors. The identification of additional Tachykinins has reopened the debate of whether more Tachykinin receptors exist. In this review, we summarize the current knowledge of Tachykinins and their receptors.
Hideo Kanaide - One of the best experts on this subject based on the ideXlab platform.
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The mechanisms for Tachykinin-induced contractions of the rabbit corpus cavernosum.
British Journal of Pharmacology, 2002Co-Authors: Ryosuke Takahashi, Junji Nishimura, Katsuya Hirano, Seiji Naito, Hideo KanaideAbstract:This study was designed to investigate the mechanisms for the contractions induced by Tachykinins (substance P (SP), neurokinin A (NKA) and neurokinin B (NKB)) in the rabbit corpus cavernosum strips, using fura-PE3 fluorimetry and α-toxin permeabilization. Tachykinins induced contractions in the rabbit corpus cavernosum in a concentration-dependent manner. The potency order was SP>NKA>NKB. The Tachykinin-induced contractions were enhanced by phosphoramidon (PPAD), an endopeptidase inhibitor, but not by Nω-nitro-L-arginine methylester (L-NAME). The NK1 receptor selective antagonist, SR 140333 significantly inhibited the Tachykinin-induced contractions. Although the NK2 receptor selective antagonist, SR 48968 alone did not influence the effects of Tachykinins, it potentiated the inhibitory effect of SR 140333. The NK3 receptor selective antagonist, SR142801 had no effect. In the rabbit corpus cavernosum, Tachykinins induced sustained increases in [Ca2+]i and tension in normal PSS, while only small transient increases in [Ca2+]i and tension were observed in Ca2+-free solution. In α-toxin permeabilized preparations, Tachykinins induced an additional force development at a constant [Ca2+]i. These results indicated that in the rabbit corpus cavernosum: (1) Tachykinins induced contractions by increasing both the [Ca2+]i and myofilament Ca2+ sensitivity; (2) The Tachykinin-induced [Ca2+]i elevations were mainly due to the Ca2+ influx; (3) Tachykinin-induced contractions were mainly mediated through the activation of NK1 receptor expressed in the rabbit corpus cavernosum smooth muscle, and affected by the endopeptidase activity and (4) Tachykinins may thus play a role in controlling the corpus cavernosum tone. British Journal of Pharmacology (2002) 137, 845–854. doi:10.1038/sj.bjp.0704938
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The mechanisms for Tachykinin‐induced contractions of the rabbit corpus cavernosum
British journal of pharmacology, 2002Co-Authors: Ryosuke Takahashi, Junji Nishimura, Katsuya Hirano, Seiji Naito, Hideo KanaideAbstract:1. This study was designed to investigate the mechanisms for the contractions induced by Tachykinins (substance P (SP), neurokinin A (NKA) and neurokinin B (NKB)) in the rabbit corpus cavernosum strips, using fura-PE3 fluorimetry and alpha-toxin permeabilization. 2. Tachykinins induced contractions in the rabbit corpus cavernosum in a concentration-dependent manner. The potency order was SP>NKA>NKB. 3. The Tachykinin-induced contractions were enhanced by phosphoramidon (PPAD), an endopeptidase inhibitor, but not by N(omega)-nitro-L-arginine methylester (L-NAME). 4. The NK(1) receptor selective antagonist, SR 140333 significantly inhibited the Tachykinin-induced contractions. Although the NK(2) receptor selective antagonist, SR 48968 alone did not influence the effects of Tachykinins, it potentiated the inhibitory effect of SR 140333. The NK(3) receptor selective antagonist, SR142801 had no effect. 5. In the rabbit corpus cavernosum, Tachykinins induced sustained increases in [Ca(2+)](i) and tension in normal PSS, while only small transient increases in [Ca(2+)](i) and tension were observed in Ca(2+)-free solution. 6. In alpha-toxin permeabilized preparations, Tachykinins induced an additional force development at a constant [Ca(2+)](i). 7. These results indicated that in the rabbit corpus cavernosum: (1) Tachykinins induced contractions by increasing both the [Ca(2+)](i) and myofilament Ca(2+) sensitivity; (2) The Tachykinin-induced [Ca(2+)](i) elevations were mainly due to the Ca(2+) influx; (3) Tachykinin-induced contractions were mainly mediated through the activation of NK(1) receptor expressed in the rabbit corpus cavernosum smooth muscle, and affected by the endopeptidase activity and (4) Tachykinins may thus play a role in controlling the corpus cavernosum tone.
Ryosuke Takahashi - One of the best experts on this subject based on the ideXlab platform.
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The mechanisms for Tachykinin-induced contractions of the rabbit corpus cavernosum.
British Journal of Pharmacology, 2002Co-Authors: Ryosuke Takahashi, Junji Nishimura, Katsuya Hirano, Seiji Naito, Hideo KanaideAbstract:This study was designed to investigate the mechanisms for the contractions induced by Tachykinins (substance P (SP), neurokinin A (NKA) and neurokinin B (NKB)) in the rabbit corpus cavernosum strips, using fura-PE3 fluorimetry and α-toxin permeabilization. Tachykinins induced contractions in the rabbit corpus cavernosum in a concentration-dependent manner. The potency order was SP>NKA>NKB. The Tachykinin-induced contractions were enhanced by phosphoramidon (PPAD), an endopeptidase inhibitor, but not by Nω-nitro-L-arginine methylester (L-NAME). The NK1 receptor selective antagonist, SR 140333 significantly inhibited the Tachykinin-induced contractions. Although the NK2 receptor selective antagonist, SR 48968 alone did not influence the effects of Tachykinins, it potentiated the inhibitory effect of SR 140333. The NK3 receptor selective antagonist, SR142801 had no effect. In the rabbit corpus cavernosum, Tachykinins induced sustained increases in [Ca2+]i and tension in normal PSS, while only small transient increases in [Ca2+]i and tension were observed in Ca2+-free solution. In α-toxin permeabilized preparations, Tachykinins induced an additional force development at a constant [Ca2+]i. These results indicated that in the rabbit corpus cavernosum: (1) Tachykinins induced contractions by increasing both the [Ca2+]i and myofilament Ca2+ sensitivity; (2) The Tachykinin-induced [Ca2+]i elevations were mainly due to the Ca2+ influx; (3) Tachykinin-induced contractions were mainly mediated through the activation of NK1 receptor expressed in the rabbit corpus cavernosum smooth muscle, and affected by the endopeptidase activity and (4) Tachykinins may thus play a role in controlling the corpus cavernosum tone. British Journal of Pharmacology (2002) 137, 845–854. doi:10.1038/sj.bjp.0704938
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The mechanisms for Tachykinin‐induced contractions of the rabbit corpus cavernosum
British journal of pharmacology, 2002Co-Authors: Ryosuke Takahashi, Junji Nishimura, Katsuya Hirano, Seiji Naito, Hideo KanaideAbstract:1. This study was designed to investigate the mechanisms for the contractions induced by Tachykinins (substance P (SP), neurokinin A (NKA) and neurokinin B (NKB)) in the rabbit corpus cavernosum strips, using fura-PE3 fluorimetry and alpha-toxin permeabilization. 2. Tachykinins induced contractions in the rabbit corpus cavernosum in a concentration-dependent manner. The potency order was SP>NKA>NKB. 3. The Tachykinin-induced contractions were enhanced by phosphoramidon (PPAD), an endopeptidase inhibitor, but not by N(omega)-nitro-L-arginine methylester (L-NAME). 4. The NK(1) receptor selective antagonist, SR 140333 significantly inhibited the Tachykinin-induced contractions. Although the NK(2) receptor selective antagonist, SR 48968 alone did not influence the effects of Tachykinins, it potentiated the inhibitory effect of SR 140333. The NK(3) receptor selective antagonist, SR142801 had no effect. 5. In the rabbit corpus cavernosum, Tachykinins induced sustained increases in [Ca(2+)](i) and tension in normal PSS, while only small transient increases in [Ca(2+)](i) and tension were observed in Ca(2+)-free solution. 6. In alpha-toxin permeabilized preparations, Tachykinins induced an additional force development at a constant [Ca(2+)](i). 7. These results indicated that in the rabbit corpus cavernosum: (1) Tachykinins induced contractions by increasing both the [Ca(2+)](i) and myofilament Ca(2+) sensitivity; (2) The Tachykinin-induced [Ca(2+)](i) elevations were mainly due to the Ca(2+) influx; (3) Tachykinin-induced contractions were mainly mediated through the activation of NK(1) receptor expressed in the rabbit corpus cavernosum smooth muscle, and affected by the endopeptidase activity and (4) Tachykinins may thus play a role in controlling the corpus cavernosum tone.
Luz Candenas - One of the best experts on this subject based on the ideXlab platform.
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Smooth muscle neurokinin-2 receptors mediate contraction in human saphenous veins
Pharmacological Research, 2011Co-Authors: Hakima Mechiche, Stanislas Grassin-delyle, Francisco M. Pinto, Amparo Buenestado, Luz Candenas, Philippe DevillierAbstract:Substance P (SP) and neurokinin A (NKA) are members of the Tachykinin peptides family. SP causes endothelial-dependant relaxation but the contractile response to Tachykinins in human vessels remains unknown. The objective was to assess the expression and the contractile effects of Tachykinins and their receptors in human saphenous veins (SV). Tachykinin expression was assessed with RT-PCR, Tachykinin receptors expression with RT-PCR and immunohistochemistry, and functional studies were performed in organ bath. Transcripts of all Tachykinin and Tachykinin receptor genes were found in SV. NK(1)-receptors were localized in both endothelial and smooth muscle layers of undistended SV, whereas they were only found in smooth muscle layers of varicose SV. The expression of NK(2)- and NK(3)-receptors was limited to the smooth muscle in both preparations. NKA induced concentration-dependent contractions in about half the varicose SV. Maximum effect reached 27.6±5.5% of 90 mM KCl and the pD(2) value was 7.3±0.2. NKA also induced the contraction of undistended veins from bypass and did not cause the relaxation of these vessels after precontraction. The NK(2)-receptor antagonist SR48968 abolished the contraction induced by NKA, and a rapid desensitization of the NK(2)-receptor was observed. In varicose SV, the agonists specific to NK(1)- or NK(3)-receptors did not cause either contraction or relaxation. The stimulation of smooth muscle NK(2)-receptors can induce the contraction of human SV. As SV is richly innervated, Tachykinins may participate in the regulation of the tone in this portion of the low pressure vascular system.
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Autocrine regulation of human sperm motility by Tachykinins.
Reproductive biology and endocrinology : RB&E, 2010Co-Authors: Francisco M. Pinto, Cristina G Ravina, Manuel Fernández-sánchez, Nerea Subirán, Antonio Cejudo-román, Jon Irazusta, Nicolas Garrido, Luz CandenasAbstract:Background: We examined the presence and function of Tachykinins and the Tachykinin-degrading enzymes neprilysin (NEP) and neprilysin-2 (NEP2) in human spermatozoa. Methods: Freshly ejaculated semen was collected from forty-eight normozoospermic human donors. We analyzed the expression of substance P, neurokinin A, neurokinin B, hemokinin-1, NEP and NEP2 in sperm cells by reversetranscriptase polymerase chain reaction (RT-PCR), western blot and immunocytochemistry assays and evaluated the effects of the neprilysin and neprilysin-2 inhibitor phosphoramidon on sperm motility in the absence and presence of Tachykinin receptor-selective antagonists. Sperm motility was measured using WHO procedures or computerassisted sperm analysis (CASA). Results: The mRNAs of the genes that encode substance P/neurokinin A (TAC1), neurokinin B (TAC3), hemokinin-1 (TAC4), neprilysin (MME) and neprilysin-2 (MMEL1) were expressed in human sperm. Immunocytochemistry studies revealed that Tachykinin and neprilysin proteins were present in spermatozoa and show specific and differential distributions. Phosphoramidon increased sperm progressive motility and its effects were reduced in the presence of the Tachykinin receptor antagonists SR140333 (NK1 receptor-selective) and SR48968 (NK2 receptor-selective) but unmodified in the presence of SR142801 (NK3 receptor-selective). Conclusion: These data show that Tachykinins are present in human spermatozoa and participate in the regulation of sperm motility. Tachykinin activity is regulated, at least in part, by neprilysins.
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Ovarian steroids regulate Tachykinin and Tachykinin receptor gene expression in the mouse uterus
Reproductive biology and endocrinology : RB&E, 2009Co-Authors: Francisco M. Pinto, Jocelyn N Pennefather, Eva N Patak, C. Oscar Pintado, Luz CandenasAbstract:Background: In the mouse uterus, pregnancy is accompanied by changes in Tachykinin and Tachykinin receptor gene expression and in the uterotonic effects of endogenous Tachykinins. In this study we have investigated whether changes in Tachykinin expression and responses are a result of changes in ovarian steroid levels. Methods: We quantified the mRNAs of Tachykinins and Tachykinin receptors in uteri from ovariectomized mice and studied their regulation in response to estrogen and progesterone using real-time quantitative RT-PCR. Early (3 h) and late (24 h) responses to estrogen were evaluated and the participation of the estrogen receptors (ER), ERalpha and ERbeta, was analyzed by treating mice with propylpyrazole triol, a selective ERalpha agonist, or diarylpropionitrile, a selective agonist of ERbeta. Results: All genes encoding Tachykinins (Tac1, Tac2 and Tac4) and Tachykinin receptors (Tacr1, Tacr2 and Tacr3) were expressed in uteri from ovariectomized mice. Estrogen increased Tac1 and Tacr1 mRNA after 3 h and decreased Tac1 and Tac4 expression after 24 h. Tac2 and Tacr3 mRNA levels were decreased by estrogen at both 3 and 24 h. Most effects of estrogen were also observed in animals treated with propylpyrazole triol. Progesterone treatment increased the levels of Tac2. Conclusion: These results show that the expression of Tachykinins and their receptors in the mouse uterus is tightly and differentially regulated by ovarian steroids. Estrogen effects are mainly mediated by ERalpha supporting an essential role for this estrogen receptor in the regulation of the tachykinergic system in the mouse uterus.