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Marcelo S Vatta - One of the best experts on this subject based on the ideXlab platform.
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involvement of endothelins in deoxycorticosterone acetate salt hypertension through the modulation of noradrenergic transmission in the rat Posterior Hypothalamus
Experimental Physiology, 2015Co-Authors: Tamara Abramoff, Liliana G Bianciotti, Maria Julia Guil, Vanina Paola Morales, Sandra Ingrid Hope, Christian Hocht, Marcelo S VattaAbstract:New Findings What is the central question of this study? Does ex vivo administration of endothelin-1 and endothelin-3 regulate noradrenergic transmission in the Posterior Hypothalamus of deoxycorticosterone acetate–salt hypertensive rats compared with normotensive rats? What is the main finding and its importance? Endothelin-1 and endothelin-3 enhanced diverse mechanisms leading to increased noradrenergic transmission in the Posterior Hypothalamus of deoxycorticosterone acetate–salt hypertensive rats. Unveiling the role of brain endothelins in hypertension would probably favour the development of new therapeutic targets for the treatment of essential hypertension, which still represents a challenging disease with high mortality. Brain catecholamines participate in diverse biological functions regulated by the Hypothalamus. We have previously reported that endothelin-1 and endothelin-3 (ET-1 and ET-3) modulate catecholaminergic activity in the anterior and Posterior Hypothalamus of normotensive rats. The aim of the present study was to evaluate the interaction between endothelins and noradrenergic transmission in the Posterior Hypothalamus of deoxycorticosterone acetate (DOCA)–salt hypertensive rats. We assessed the effects of ET-1 and ET-3 on tyrosine hydroxylase activity and expression, neuronal noradrenaline (NA) release, neuronal NA transporter (NAT) activity and expression, monoamine oxidase activity and NA endogenous content and utilization (as a marker of turnover) in the Posterior Hypothalamus of DOCA–salt hypertensive rats. In addition, levels of ETA and ETB receptors were assayed in normotensive and hypertensive rats. Results showed that tyrosine hydroxylase activity and total and phosphorylated levels, NAT activity and content, NA release, monoamine oxidase activity and NA utilization were increased in DOCA–salt rats. Both ET-1 and ET-3 further enhanced all noradrenergic parameters except for total tyrosine hydroxylase level and NA endogenous content and utilization. The expression of ETA receptors was increased in the Posterior Hypothalamus of DOCA–salt rats, but ETB receptors showed no changes. These results show that ET-1 and ET-3 upregulate noradrenergic activity in the Posterior Hypothalamus of DOCA–salt hypertensive rats. Our findings suggest that the interaction between noradrenergic transmission and the endothelinergic system in the Posterior Hypothalamus may be involved in the development and/or maintenance of hypertension in this animal model.
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endothelin 1 and 3 modulate the neuronal norepinephrine transporter through multiple signalling pathways in the rat Posterior Hypothalamus
Neurochemistry International, 2010Co-Authors: Sandra Ingrid Hope, Liliana G Bianciotti, Sabrina Laura Nabhen, Celeste Soria, Marcelo S VattaAbstract:We have previously reported that endothelin-1 and -3 modulate different steps of noradrenergic transmission in the Hypothalamus. We showed that endothelins modify neuronal norepinephrine transport activity through the regulation of the kinetic constant and internalization. In the present work we sought to define the endothelin receptors and intracellular mechanisms involved in the down-regulation of neuronal norepinephrine uptake induced by endothelin-1 and -3 in the rat Posterior hypothalamic region. Results showed that endothelin-1 reduced norepinephrine uptake through ET(B) receptors, whereas endothelin-3 through a non-conventional or atypical endothelin receptor. In both cases, the effect on norepinephrine uptake was coupled to protein kinase A and C as well as nitric oxide pathways. However, neither protein kinase G nor intracellular or extracellular calcium and calcium/calmodulin-dependent protein kinase II were involved. In addition, the same intracellular mechanisms participated in the reduction of nisoxetine binding (norepinephrine transporter internalization index) induced by both endothelins. Present findings reveal the underlying mechanisms involved in the regulation of the neuronal norepinephrine transporter by endothelins and further support the role of these peptides in the modulation of noradrenergic transmission at the presynaptic nerve endings in the Posterior Hypothalamus.
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Regulation of the neuronal norepinephrine transporter by endothelin-1 and -3 in the rat anterior and Posterior Hypothalamus.
Neurochemistry international, 2008Co-Authors: Sandra I Hope, Josefina Schmipp, Andres H Rossi, Liliana G Bianciotti, Marcelo S VattaAbstract:We previously reported that endothelin-1 and endothelin-3 modulate norepinephrine neuronal release and tyrosine hydroxylase activity and expression in the Hypothalamus. In the present study we sought to establish the role of endothelin-1 and -3 in the regulation of norepinephrine uptake in the anterior and Posterior Hypothalamus. Results showed that in the anterior Hypothalamus endothelin-3 increased neuronal norepinephrine uptake whereas endothelin-1 decreased it. Conversely, in the Posterior hypothalamic region both endothelins diminished the neuronal uptake of the amine. Endothelins response was concentration dependent and maintained at all studied times. Endothelins also modified the kinetic and internalization of the NE neuronal transporter. In the anterior hypothalamic region endothelin-3 increased the V(max) and the B(max) whereas endothelin-1 decreased them. However, in the Posterior hypothalamic region both endothelins diminished the V(max) as well as B(max). Neither endothelin-1 nor endothelin-3 modified neuronal norepinephrine transporter K(d) in the studied hypothalamic regions. These findings support that in the Posterior hypothalamic region both endothelins diminished neuronal norepinephrine transporter activity by reducing the amine transporter expression on the plasmatic membrane. Conversely, in the anterior hypothalamic region endothelin-3 enhanced neuronal norepinephrine transporter activity by increasing the expression of the transporter on the presynaptic membrane, whereas endothelin-1 induced the opposite effect. Present results permit us to conclude that both endothelins play an important role in the regulation of norepinephrine neurotransmission at the presynaptic nerve endings in the Hypothalamus.
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short term regulation of tyrosine hydroxylase activity and expression by endothelin 1 and endothelin 3 in the rat Posterior Hypothalamus
Regulatory Peptides, 2007Co-Authors: Guadalupe Perfume, Liliana G Bianciotti, Sandra Ingrid Hope, Carolina Morgazo, Sabrina Laura Nabhen, Agustina Batistone, Marcelo S VattaAbstract:Brain catecholamines are involved in several biological functions regulated by the Hypothalamus. We have previously reported that endothelin-1 and -3 (ET-1 and ET-3) modulate norepinephrine release in the anterior and Posterior Hypothalamus. As tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, the aim of the present work was to investigate the effects of ET-1 and ET-3 on TH activity, total enzyme level and the phosphorylated forms of TH in the rat Posterior Hypothalamus. Results showed that ET-1 and ET-3 diminished TH activity but the response was abolished by both selective ET(A) and ET(B) antagonists (BQ-610 and BQ-788, respectively). In addition ET(A) and ET(B) selective agonists (sarafotoxin S6b and IRL-1620, respectively) failed to affect TH activity. In order to investigate the intracellular signaling coupled to endothelins (ETs) response, nitric oxide (NO), phosphoinositide, cAMP/PKA and CaMK-II pathways were studied. Results showed that N(omega)-nitro-l-arginine methyl ester and 7-nitroindazole (NO synthase and neuronal NO synthase inhibitors, respectively), 1H-[1,2,4]-oxadiazolo[4,3-alpha]quinozalin-1-one and KT-5823 (soluble guanylyl cyclase, and PKG inhibitors, respectively) inhibited ETs effect on TH activity. Further, sodium nitroprusside and 8-bromoguanosine-3',5'-cyclic monophosphate (NO donor and cGMP analog, respectively) mimicked ETs response. ETs-induced reduction of TH activity was not affected by a PKA inhibitor but it was abolished by PLC, PKC and CaMK-II inhibitors as well as by an IP(3) receptor antagonist. On the other hand, both ETs did not modify TH total level but reduced the phosphorylation of serine residues of the enzyme at positions 19, 31 and 40. Present results suggest that ET-1 and ET-3 diminished TH activity through an atypical ET or ET(C) receptor coupled to the NO/cGMP/PKG, phosphoinositide and CaMK-II pathways. Furthermore, TH diminished activity may result from the reduction of the phosphorylated sites of the enzyme without changes in its total level. Taken jointly present and previous results support that ET-1 and ET-3 may play a relevant role in the modulation of catecholaminergic neurotransmission in the Posterior Hypothalamus of the rat.
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modulatory effect of endothelin 1 and 3 on neuronal norepinephrine release in the rat Posterior Hypothalamus
Regulatory Peptides, 2004Co-Authors: Andrea S Di Nunzio, Liliana G Bianciotti, Guillermina Legaz, Valeria Rodano, Marcelo S VattaAbstract:Abstract Based upon the existence of high density of ET-receptors on catecholaminergic neurons of the Hypothalamus, we studied the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on neuronal norepinephrine (NE) release in the rat Posterior Hypothalamus. The intracellular pathways and receptors involved were also investigated. Neuronal NE release was enhanced by ET-1 and ET-3 (10 ηM). The selective antagonists of subtype A and B ET receptors (ET A , ET B ) (100 ηM BQ-610 and 100 ηM BQ-788, respectively) abolished the increase induced by ET-1 but not by ET-3. The PLC inhibitor, U73122 (10 μM), abolished ET-1 and ET-3 response. GF-109203X (100 ηM) (PKC inhibitor) blocked the increase in NE release produced by ET-3 and partially blocked ET-1 response. The inositol 1,4,5-trisphosphate-induced calcium release inhibitor, 42 μM 2-APB, inhibited the stimulatory effect induced by ET-3 but not by ET-1. The PKA inhibitor, 500 ηM H-89, blocked the increase in neuronal NE release evoked by ET-1 but not by ET-3. Our results showed that ET-1 as well as ET-3 displayed an excitatory neuromodulatory effect on neuronal NE release in the rat Posterior Hypothalamus. ET-1 through an atypical ET A or ET B receptor activated the PLC/PKC signalling pathway as well as the cAMP pathway, whereas ET-3 through a non-ET A /non-ET B receptor activated the phosphoinositide pathway. Both ETs would enhance the sympathoexcitatory response elicited by the Posterior Hypothalamus and thus participate in cardiovascular regulation.
Hyun Chul Koh - One of the best experts on this subject based on the ideXlab platform.
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involvement of no and katp channel in adenosine a2b receptors induced cardiovascular regulation in the Posterior Hypothalamus of rats
Journal of Cardiovascular Pharmacology, 2009Co-Authors: Tae Kyung Lee, Hyun Chul KohAbstract:Previous reports have suggested that the Posterior hypothalamic adenosine A2 receptors may play a role in central cardiovascular regulation. In this study, we examined the influence of Posterior hypothalamic adenosine A2B receptors on the regulation of blood pressure and heart rate. Drugs were injected into the Posterior Hypothalamus of anesthetized, artificially ventilated, male Sprague-Dawley rats. Four nanomoles of 5'-N-ethylcarboxamidoadenosine (NECA), an adenosine A 2A receptor agonist, decreased arterial blood pressure and heart rate, whereas 5 nmol of alloxazine, an adenosine A2B receptor antagonist, blocked the depressor and bradycardiac effects of 4 nmol NECA. We examined the role of nitric oxide (NO) and K+ channels on cardiovascular regulation by adenosine A2B receptors in the Posterior Hypothalamus. Pretreatment with 40 nmol of NG-nitro-L-arginine methyl ester, a NO synthase inhibitor, significantly attenuated the effects of NECA, and 10 nmol of sodium nitroprusside, a NO releaser, strengthened the action of drug. In addition, Posterior hypothalamic administration of 20 nmol of glipizide, an K ATP blocker, blocked the cardiovascular depression elicited by NECA. These results suggest that NO mediates cardiovascular regulation by activation of A2B receptors in the Posterior Hypothalamus. Additionally, ATP-sensitive K+ channels modulate the action of adenosine A2B receptors.
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involvement of guanylate cyclase in the cardiovascular response induced by adenosine a2b receptor stimulation in the Posterior Hypothalamus of the anesthetized rats
Autonomic Neuroscience: Basic and Clinical, 2007Co-Authors: Min Jeong Kang, Hyun Chul KohAbstract:Abstract Cardiovascular inhibitory effects induced by the Posterior hypothalamic adenosine A 2 receptors were suggested by our previous reports. In this experiment, we examined the influence of the Posterior hypothalamic adenosine A 2B receptors on central cardiovascular regulation of blood pressure (BP) and heart rate (HR). Posterior hypothalamic injection of drugs was performed in anesthetized, artificially ventilated male Sprague–Dawley rats. Injection of 5′-( N -cyclopropyl)-carboxamidoadenosine (CPCA; 2 nmol), an adenosine A 2 receptor agonist, showed the decrease of arterial blood pressure and heart rate, and the alloxazine, an adenosine A 2B receptor antagonist, partially blocked the depressor and bradycardiac effects of CPCA (2 nmol). To examine the role of adenosine A 2B receptors among the adenosine A 2 subtypes, we applied the 5′- N -Ethylcarboxamidoadenosine (NECA), an adenosine A 2B receptor agonist, to the Posterior Hypothalamus. Injection of NECA (1, 4 and 8 nmol) produced a dose-dependent decrease of arterial blood pressure and HR. Pretreatment with alloxazine (5 nmol) partially blocked the depressor and bradycardiac effects of NECA (4 nmol). Also, pretreatment with LY-83,583 (5 nmol), a soluble guanylate cyclase inhibitor, attenuated the depressor and bradycardiac effects of NECA (4 nmol). However, pretreatment with MDL-12,330 (10 nmol), an adenylate cyclase inhibitor, did not affect these effects of NECA (4 nmol). These results suggest that adenosine A 2B receptor in the Posterior Hypothalamus plays an inhibitory role in central cardiovascular regulation, and that guanylate cyclase mediates the depressor and bradycardiac actions of adenosine A 2B receptors.
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the involvement of nitric oxide on the adenosine a2 receptor induced cardiovascular inhibitory responses in the Posterior Hypothalamus of rats
Neuroscience Letters, 2002Co-Authors: Man Sung Song, Kyoung Ah Shin, Ju Seop Kang, Chang Ho Lee, In Chul Shin, Soojin Lee, Hyun Chul KohAbstract:This study was performed to investigate the putative relationship between nitric oxide (NO) and adenosine A(2) receptors on central cardiovascular regulation in the Posterior Hypothalamus of rats. Posterior hypothalamic injection of drugs was performed in anesthetized, artificially ventilated male Sprague-Dawley rats. Injection of adenosine A(2) receptor agonist 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 1, 2 and 5 nmol) produced a dose-dependent decrease of blood pressure and heart rate. Pretreatment with adenosine A(2) receptor antagonist 3,7-dimethyl-1-propargylxanthine (10 nmol) blocked the depressor and bradycardiac effects of CPCA (5 nmol). Pretreatment with soluble guanylate cyclase inhibitor LY-83,583 (5 nmol) attenuated the depressor and bradycardiac effects of CPCA (5 nmol). In addition, pretreatment with NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (40 nmol) attenuated the depressor and bradycardiac responses of CPCA (5 nmol). These results suggest that adenosine A(2) receptor in the Posterior Hypothalamus plays an inhibitory role in central cardiovascular regulation and that NO participates in the inhibitory response induced by adenosine A(2) receptor stimulation in the Posterior Hypothalamus.
Liliana G Bianciotti - One of the best experts on this subject based on the ideXlab platform.
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involvement of endothelins in deoxycorticosterone acetate salt hypertension through the modulation of noradrenergic transmission in the rat Posterior Hypothalamus
Experimental Physiology, 2015Co-Authors: Tamara Abramoff, Liliana G Bianciotti, Maria Julia Guil, Vanina Paola Morales, Sandra Ingrid Hope, Christian Hocht, Marcelo S VattaAbstract:New Findings What is the central question of this study? Does ex vivo administration of endothelin-1 and endothelin-3 regulate noradrenergic transmission in the Posterior Hypothalamus of deoxycorticosterone acetate–salt hypertensive rats compared with normotensive rats? What is the main finding and its importance? Endothelin-1 and endothelin-3 enhanced diverse mechanisms leading to increased noradrenergic transmission in the Posterior Hypothalamus of deoxycorticosterone acetate–salt hypertensive rats. Unveiling the role of brain endothelins in hypertension would probably favour the development of new therapeutic targets for the treatment of essential hypertension, which still represents a challenging disease with high mortality. Brain catecholamines participate in diverse biological functions regulated by the Hypothalamus. We have previously reported that endothelin-1 and endothelin-3 (ET-1 and ET-3) modulate catecholaminergic activity in the anterior and Posterior Hypothalamus of normotensive rats. The aim of the present study was to evaluate the interaction between endothelins and noradrenergic transmission in the Posterior Hypothalamus of deoxycorticosterone acetate (DOCA)–salt hypertensive rats. We assessed the effects of ET-1 and ET-3 on tyrosine hydroxylase activity and expression, neuronal noradrenaline (NA) release, neuronal NA transporter (NAT) activity and expression, monoamine oxidase activity and NA endogenous content and utilization (as a marker of turnover) in the Posterior Hypothalamus of DOCA–salt hypertensive rats. In addition, levels of ETA and ETB receptors were assayed in normotensive and hypertensive rats. Results showed that tyrosine hydroxylase activity and total and phosphorylated levels, NAT activity and content, NA release, monoamine oxidase activity and NA utilization were increased in DOCA–salt rats. Both ET-1 and ET-3 further enhanced all noradrenergic parameters except for total tyrosine hydroxylase level and NA endogenous content and utilization. The expression of ETA receptors was increased in the Posterior Hypothalamus of DOCA–salt rats, but ETB receptors showed no changes. These results show that ET-1 and ET-3 upregulate noradrenergic activity in the Posterior Hypothalamus of DOCA–salt hypertensive rats. Our findings suggest that the interaction between noradrenergic transmission and the endothelinergic system in the Posterior Hypothalamus may be involved in the development and/or maintenance of hypertension in this animal model.
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endothelin 1 and 3 modulate the neuronal norepinephrine transporter through multiple signalling pathways in the rat Posterior Hypothalamus
Neurochemistry International, 2010Co-Authors: Sandra Ingrid Hope, Liliana G Bianciotti, Sabrina Laura Nabhen, Celeste Soria, Marcelo S VattaAbstract:We have previously reported that endothelin-1 and -3 modulate different steps of noradrenergic transmission in the Hypothalamus. We showed that endothelins modify neuronal norepinephrine transport activity through the regulation of the kinetic constant and internalization. In the present work we sought to define the endothelin receptors and intracellular mechanisms involved in the down-regulation of neuronal norepinephrine uptake induced by endothelin-1 and -3 in the rat Posterior hypothalamic region. Results showed that endothelin-1 reduced norepinephrine uptake through ET(B) receptors, whereas endothelin-3 through a non-conventional or atypical endothelin receptor. In both cases, the effect on norepinephrine uptake was coupled to protein kinase A and C as well as nitric oxide pathways. However, neither protein kinase G nor intracellular or extracellular calcium and calcium/calmodulin-dependent protein kinase II were involved. In addition, the same intracellular mechanisms participated in the reduction of nisoxetine binding (norepinephrine transporter internalization index) induced by both endothelins. Present findings reveal the underlying mechanisms involved in the regulation of the neuronal norepinephrine transporter by endothelins and further support the role of these peptides in the modulation of noradrenergic transmission at the presynaptic nerve endings in the Posterior Hypothalamus.
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Regulation of the neuronal norepinephrine transporter by endothelin-1 and -3 in the rat anterior and Posterior Hypothalamus.
Neurochemistry international, 2008Co-Authors: Sandra I Hope, Josefina Schmipp, Andres H Rossi, Liliana G Bianciotti, Marcelo S VattaAbstract:We previously reported that endothelin-1 and endothelin-3 modulate norepinephrine neuronal release and tyrosine hydroxylase activity and expression in the Hypothalamus. In the present study we sought to establish the role of endothelin-1 and -3 in the regulation of norepinephrine uptake in the anterior and Posterior Hypothalamus. Results showed that in the anterior Hypothalamus endothelin-3 increased neuronal norepinephrine uptake whereas endothelin-1 decreased it. Conversely, in the Posterior hypothalamic region both endothelins diminished the neuronal uptake of the amine. Endothelins response was concentration dependent and maintained at all studied times. Endothelins also modified the kinetic and internalization of the NE neuronal transporter. In the anterior hypothalamic region endothelin-3 increased the V(max) and the B(max) whereas endothelin-1 decreased them. However, in the Posterior hypothalamic region both endothelins diminished the V(max) as well as B(max). Neither endothelin-1 nor endothelin-3 modified neuronal norepinephrine transporter K(d) in the studied hypothalamic regions. These findings support that in the Posterior hypothalamic region both endothelins diminished neuronal norepinephrine transporter activity by reducing the amine transporter expression on the plasmatic membrane. Conversely, in the anterior hypothalamic region endothelin-3 enhanced neuronal norepinephrine transporter activity by increasing the expression of the transporter on the presynaptic membrane, whereas endothelin-1 induced the opposite effect. Present results permit us to conclude that both endothelins play an important role in the regulation of norepinephrine neurotransmission at the presynaptic nerve endings in the Hypothalamus.
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short term regulation of tyrosine hydroxylase activity and expression by endothelin 1 and endothelin 3 in the rat Posterior Hypothalamus
Regulatory Peptides, 2007Co-Authors: Guadalupe Perfume, Liliana G Bianciotti, Sandra Ingrid Hope, Carolina Morgazo, Sabrina Laura Nabhen, Agustina Batistone, Marcelo S VattaAbstract:Brain catecholamines are involved in several biological functions regulated by the Hypothalamus. We have previously reported that endothelin-1 and -3 (ET-1 and ET-3) modulate norepinephrine release in the anterior and Posterior Hypothalamus. As tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, the aim of the present work was to investigate the effects of ET-1 and ET-3 on TH activity, total enzyme level and the phosphorylated forms of TH in the rat Posterior Hypothalamus. Results showed that ET-1 and ET-3 diminished TH activity but the response was abolished by both selective ET(A) and ET(B) antagonists (BQ-610 and BQ-788, respectively). In addition ET(A) and ET(B) selective agonists (sarafotoxin S6b and IRL-1620, respectively) failed to affect TH activity. In order to investigate the intracellular signaling coupled to endothelins (ETs) response, nitric oxide (NO), phosphoinositide, cAMP/PKA and CaMK-II pathways were studied. Results showed that N(omega)-nitro-l-arginine methyl ester and 7-nitroindazole (NO synthase and neuronal NO synthase inhibitors, respectively), 1H-[1,2,4]-oxadiazolo[4,3-alpha]quinozalin-1-one and KT-5823 (soluble guanylyl cyclase, and PKG inhibitors, respectively) inhibited ETs effect on TH activity. Further, sodium nitroprusside and 8-bromoguanosine-3',5'-cyclic monophosphate (NO donor and cGMP analog, respectively) mimicked ETs response. ETs-induced reduction of TH activity was not affected by a PKA inhibitor but it was abolished by PLC, PKC and CaMK-II inhibitors as well as by an IP(3) receptor antagonist. On the other hand, both ETs did not modify TH total level but reduced the phosphorylation of serine residues of the enzyme at positions 19, 31 and 40. Present results suggest that ET-1 and ET-3 diminished TH activity through an atypical ET or ET(C) receptor coupled to the NO/cGMP/PKG, phosphoinositide and CaMK-II pathways. Furthermore, TH diminished activity may result from the reduction of the phosphorylated sites of the enzyme without changes in its total level. Taken jointly present and previous results support that ET-1 and ET-3 may play a relevant role in the modulation of catecholaminergic neurotransmission in the Posterior Hypothalamus of the rat.
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modulatory effect of endothelin 1 and 3 on neuronal norepinephrine release in the rat Posterior Hypothalamus
Regulatory Peptides, 2004Co-Authors: Andrea S Di Nunzio, Liliana G Bianciotti, Guillermina Legaz, Valeria Rodano, Marcelo S VattaAbstract:Abstract Based upon the existence of high density of ET-receptors on catecholaminergic neurons of the Hypothalamus, we studied the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) on neuronal norepinephrine (NE) release in the rat Posterior Hypothalamus. The intracellular pathways and receptors involved were also investigated. Neuronal NE release was enhanced by ET-1 and ET-3 (10 ηM). The selective antagonists of subtype A and B ET receptors (ET A , ET B ) (100 ηM BQ-610 and 100 ηM BQ-788, respectively) abolished the increase induced by ET-1 but not by ET-3. The PLC inhibitor, U73122 (10 μM), abolished ET-1 and ET-3 response. GF-109203X (100 ηM) (PKC inhibitor) blocked the increase in NE release produced by ET-3 and partially blocked ET-1 response. The inositol 1,4,5-trisphosphate-induced calcium release inhibitor, 42 μM 2-APB, inhibited the stimulatory effect induced by ET-3 but not by ET-1. The PKA inhibitor, 500 ηM H-89, blocked the increase in neuronal NE release evoked by ET-1 but not by ET-3. Our results showed that ET-1 as well as ET-3 displayed an excitatory neuromodulatory effect on neuronal NE release in the rat Posterior Hypothalamus. ET-1 through an atypical ET A or ET B receptor activated the PLC/PKC signalling pathway as well as the cAMP pathway, whereas ET-3 through a non-ET A /non-ET B receptor activated the phosphoinositide pathway. Both ETs would enhance the sympathoexcitatory response elicited by the Posterior Hypothalamus and thus participate in cardiovascular regulation.
Angelo Franzini - One of the best experts on this subject based on the ideXlab platform.
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exploring the brain through Posterior Hypothalamus surgery for aggressive behavior
Neurosurgical Focus, 2017Co-Authors: Michele Rizzi, Angelo Franzini, Andrea Trezza, Giuseppe Messina, Alessandro De Benedictis, Carlo Efisio MarrasAbstract:Neurological surgery offers an opportunity to study brain functions, through either resection or implanted neuromodulation devices. Pathological aggressive behavior in patients with intellectual disability is a frequent condition that is difficult to treat using either supportive care or pharmacological therapy. The bulk of the laboratory studies performed throughout the 19th century enabled the formulation of hypotheses on brain circuits involved in the generation of emotions. Aggressive behavior was also studied extensively. Lesional radiofrequency surgery of the Posterior Hypothalamus, which peaked in the 1970s, was shown to be an effective therapy in many reported series. As with other surgical procedures for the treatment of psychiatric disorders, however, this therapy was abandoned for many reasons, including the risk of its misuse. Deep brain stimulation (DBS) offers the possibility of treating neurological and psychoaffective disorders through relatively reversible and adaptable therapy. Deep brain stimulation of the Posterior Hypothalamus was proposed and performed successfully in 2005 as a treatment for aggressive behavior. Other groups reported positive outcomes using target and parameter settings similar to those of the original study. Both the lesional and DBS approaches enabled researchers to explore the role of the Posterior Hypothalamus (or Posterior hypothalamic area) in the autonomic and emotional systems.
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effect on sleep of Posterior Hypothalamus stimulation in cluster headache
Headache, 2007Co-Authors: Roberto Vetrugno, Giulia Pierangeli, Massimo Leone, Gennaro Bussone, Angelo Franzini, Giovanni Brogli, Roberto Dangelo, Pietro Cortelli, Pasquale MontagnaAbstract:Objective To evaluate the structure and quality of sleep and the circadian rhythm of body core temperature (BcT degrees ) in patients with drug-resistant chronic cluster headache (CH) before and during deep brain stimulation (DBS) of the Posterior Hypothalamus. Background Chronic CH is a severe primary headache and frequently associated with disturbances in sleep. Posterior Hypothalamus DBS is performed as an effective treatment of drug-resistant chronic CH. The effects of Posterior Hypothalamus DBS on sleep and the circadian rhythm of BcT degrees are unknown. Methods Three male patients with chronic drug-resistant CH underwent 48-hour consecutive polysomnography (PSG) by means of the VITAPORT system with determination of BcT degrees by means of a rectal probe. Recordings were done before electrode implantation in the Posterior Hypothalamus and after optimized DBS of Posterior Hypothalamus. Results Before electrode implantation PSG showed nocturnal CH attacks, reduced sleep efficiency, fragmented sleep and increased periodic limb movements in sleep (PLMS). During DBS nocturnal CH attacks were abolished and sleep efficiency and PLMS improved. BcT degrees circadian rhythm was normal both before and during DBS. Conclusions Our data show that DBS of Posterior Hypothalamus in drug-resistant chronic CH is effective in curtailing nocturnal CH attacks, and is associated with improved sleep structure and quality. Chronic CH displays a normal circadian rhythm of BcT degrees, unchanged during hypothalamic DBS.
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update on neurosurgical treatment of chronic trigeminal autonomic cephalalgias and atypical facial pain with deep brain stimulation of Posterior Hypothalamus results and comments
Neurological Sciences, 2007Co-Authors: Giovanni Broggi, Angelo Franzini, M Leone, G BussoneAbstract:The objective of this study is to describe the therapeutic effect and the technical and surgical problems of deep brain stimulation (DBS) of the Posterior Hypothalamus over seven years, for treatment of chronic trigeminal autonomic cephalalgias and atypical facial pain. We report a surgical series of 20 patients that underwent DBS of the Posterior Hypothalamus. This series includes 16 patients with chronic cluster headache (CH), one patient with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and three patients with atypical facial pain. All patients of this series were resistant to any pharmacological and conservative treatment. The stimulated target was the same in the whole series even though stereotactic coordinates of the target referred to the midcommissural point differ slight in the Y anteroPosterior value due to individual anatomical variability. The commissures based reference system was adapted to individual anatomical landmarks of the brainstem adding to the registration a third reference point below the commissural plane. The stimulation parameters of unipolar stimulation were similar in the whole series: 180 Hz, 60 μs, 1–3 V. In the CH series, at five years follow-up the percentage of total number of days free from pain attacks improved from 1%–2% to 71%. Ten patients of this series had a complete and persistent pain-free state at 18 months follow-up and the patient with SUNCT has complete pain relief. In the three patients with atypical facial pain, the neurostimulation procedure was absolutely unsuccessful. DBS of the Posterior Hypothalamus produced a significant and marked reduction of pain bouts in CH patients and in the SUNCT patient. The attempts to treat atypical facial pain in three patients failed.
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spontaneous neuronal activity of the Posterior Hypothalamus in trigeminal autonomic cephalalgias
Neurological Sciences, 2007Co-Authors: Roberto Cordella, Gennaro Bussone, Angelo Franzini, F Carella, M Leone, Giovanni Broggi, Alberto AlbaneseAbstract:Microrecordings of three neurons were obtained at the target site in three patients with trigeminal autonomic cephalalgias who were implanted with deep brain stimulators in the Posterior Hypothalamus. Two patients had chronic cluster headache, one short unilateral neuralgiform headache with conjunctival injection and tearing. Average firing rate was around 24 spikes/s. All neurons were firing randomly, and for most of the recordings in tonic fashion. In one patient, tactile stimulation of the ophthalmic branch, contralateral to the recording site, decreased the firing rate. Neuronal activity in these patients was similar to that reported in animal studies of the Posterior Hypothalamus. Positioning deep brain stimulators in the Posterior Hypothalamus may offer a tool to better characterise the activity of this part of the brain in humans.
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stimulation of the Posterior Hypothalamus for treatment of chronic intractable cluster headaches first reported series
Neurosurgery, 2003Co-Authors: Angelo Franzini, Massimo Leone, Paolo Ferroli, Giovanni BroggiAbstract:OBJECTIVETo describe the results of deep brain stimulation of the ipsilateral Posterior Hypothalamus for the treatment of drug-resistant chronic cluster headaches (CHs). A technique for electrode placement is reported.METHODSBecause recent functional studies suggested hypothalamic dysfunction as the
Sandra Ingrid Hope - One of the best experts on this subject based on the ideXlab platform.
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involvement of endothelins in deoxycorticosterone acetate salt hypertension through the modulation of noradrenergic transmission in the rat Posterior Hypothalamus
Experimental Physiology, 2015Co-Authors: Tamara Abramoff, Liliana G Bianciotti, Maria Julia Guil, Vanina Paola Morales, Sandra Ingrid Hope, Christian Hocht, Marcelo S VattaAbstract:New Findings What is the central question of this study? Does ex vivo administration of endothelin-1 and endothelin-3 regulate noradrenergic transmission in the Posterior Hypothalamus of deoxycorticosterone acetate–salt hypertensive rats compared with normotensive rats? What is the main finding and its importance? Endothelin-1 and endothelin-3 enhanced diverse mechanisms leading to increased noradrenergic transmission in the Posterior Hypothalamus of deoxycorticosterone acetate–salt hypertensive rats. Unveiling the role of brain endothelins in hypertension would probably favour the development of new therapeutic targets for the treatment of essential hypertension, which still represents a challenging disease with high mortality. Brain catecholamines participate in diverse biological functions regulated by the Hypothalamus. We have previously reported that endothelin-1 and endothelin-3 (ET-1 and ET-3) modulate catecholaminergic activity in the anterior and Posterior Hypothalamus of normotensive rats. The aim of the present study was to evaluate the interaction between endothelins and noradrenergic transmission in the Posterior Hypothalamus of deoxycorticosterone acetate (DOCA)–salt hypertensive rats. We assessed the effects of ET-1 and ET-3 on tyrosine hydroxylase activity and expression, neuronal noradrenaline (NA) release, neuronal NA transporter (NAT) activity and expression, monoamine oxidase activity and NA endogenous content and utilization (as a marker of turnover) in the Posterior Hypothalamus of DOCA–salt hypertensive rats. In addition, levels of ETA and ETB receptors were assayed in normotensive and hypertensive rats. Results showed that tyrosine hydroxylase activity and total and phosphorylated levels, NAT activity and content, NA release, monoamine oxidase activity and NA utilization were increased in DOCA–salt rats. Both ET-1 and ET-3 further enhanced all noradrenergic parameters except for total tyrosine hydroxylase level and NA endogenous content and utilization. The expression of ETA receptors was increased in the Posterior Hypothalamus of DOCA–salt rats, but ETB receptors showed no changes. These results show that ET-1 and ET-3 upregulate noradrenergic activity in the Posterior Hypothalamus of DOCA–salt hypertensive rats. Our findings suggest that the interaction between noradrenergic transmission and the endothelinergic system in the Posterior Hypothalamus may be involved in the development and/or maintenance of hypertension in this animal model.
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endothelin 1 and 3 modulate the neuronal norepinephrine transporter through multiple signalling pathways in the rat Posterior Hypothalamus
Neurochemistry International, 2010Co-Authors: Sandra Ingrid Hope, Liliana G Bianciotti, Sabrina Laura Nabhen, Celeste Soria, Marcelo S VattaAbstract:We have previously reported that endothelin-1 and -3 modulate different steps of noradrenergic transmission in the Hypothalamus. We showed that endothelins modify neuronal norepinephrine transport activity through the regulation of the kinetic constant and internalization. In the present work we sought to define the endothelin receptors and intracellular mechanisms involved in the down-regulation of neuronal norepinephrine uptake induced by endothelin-1 and -3 in the rat Posterior hypothalamic region. Results showed that endothelin-1 reduced norepinephrine uptake through ET(B) receptors, whereas endothelin-3 through a non-conventional or atypical endothelin receptor. In both cases, the effect on norepinephrine uptake was coupled to protein kinase A and C as well as nitric oxide pathways. However, neither protein kinase G nor intracellular or extracellular calcium and calcium/calmodulin-dependent protein kinase II were involved. In addition, the same intracellular mechanisms participated in the reduction of nisoxetine binding (norepinephrine transporter internalization index) induced by both endothelins. Present findings reveal the underlying mechanisms involved in the regulation of the neuronal norepinephrine transporter by endothelins and further support the role of these peptides in the modulation of noradrenergic transmission at the presynaptic nerve endings in the Posterior Hypothalamus.
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short term regulation of tyrosine hydroxylase activity and expression by endothelin 1 and endothelin 3 in the rat Posterior Hypothalamus
Regulatory Peptides, 2007Co-Authors: Guadalupe Perfume, Liliana G Bianciotti, Sandra Ingrid Hope, Carolina Morgazo, Sabrina Laura Nabhen, Agustina Batistone, Marcelo S VattaAbstract:Brain catecholamines are involved in several biological functions regulated by the Hypothalamus. We have previously reported that endothelin-1 and -3 (ET-1 and ET-3) modulate norepinephrine release in the anterior and Posterior Hypothalamus. As tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, the aim of the present work was to investigate the effects of ET-1 and ET-3 on TH activity, total enzyme level and the phosphorylated forms of TH in the rat Posterior Hypothalamus. Results showed that ET-1 and ET-3 diminished TH activity but the response was abolished by both selective ET(A) and ET(B) antagonists (BQ-610 and BQ-788, respectively). In addition ET(A) and ET(B) selective agonists (sarafotoxin S6b and IRL-1620, respectively) failed to affect TH activity. In order to investigate the intracellular signaling coupled to endothelins (ETs) response, nitric oxide (NO), phosphoinositide, cAMP/PKA and CaMK-II pathways were studied. Results showed that N(omega)-nitro-l-arginine methyl ester and 7-nitroindazole (NO synthase and neuronal NO synthase inhibitors, respectively), 1H-[1,2,4]-oxadiazolo[4,3-alpha]quinozalin-1-one and KT-5823 (soluble guanylyl cyclase, and PKG inhibitors, respectively) inhibited ETs effect on TH activity. Further, sodium nitroprusside and 8-bromoguanosine-3',5'-cyclic monophosphate (NO donor and cGMP analog, respectively) mimicked ETs response. ETs-induced reduction of TH activity was not affected by a PKA inhibitor but it was abolished by PLC, PKC and CaMK-II inhibitors as well as by an IP(3) receptor antagonist. On the other hand, both ETs did not modify TH total level but reduced the phosphorylation of serine residues of the enzyme at positions 19, 31 and 40. Present results suggest that ET-1 and ET-3 diminished TH activity through an atypical ET or ET(C) receptor coupled to the NO/cGMP/PKG, phosphoinositide and CaMK-II pathways. Furthermore, TH diminished activity may result from the reduction of the phosphorylated sites of the enzyme without changes in its total level. Taken jointly present and previous results support that ET-1 and ET-3 may play a relevant role in the modulation of catecholaminergic neurotransmission in the Posterior Hypothalamus of the rat.
