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J P Huidobrotoro - One of the best experts on this subject based on the ideXlab platform.
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pharmacological characterization of the inhibitory activity of βh endorphin βh ep arg9 19 24 28 29 βh ep gln8 gly31 βh ep gly gly nh2 in the Neuroeffector Junction of the mouse vas deferens
Journal of Pharmacy and Pharmacology, 2011Co-Authors: R Valenzuela, J P HuidobrotoroAbstract:The inhibitory opioid activities of beta h-endorphin (beta h-EP), its structurally related peptide analogues [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 (Gly-Gly-beta h-EP), [Arg9,19,24,28,29]-beta h-EP (Arg-beta h-EP) and methionine enkephalin have been examined in the electrically stimulated mouse vas deferens bioassay. All four peptides behaved as full agonists; methionine enkephalin was the most potent followed by Arg-beta h-EP, beta h-EP and Gly-Gly-beta h-EP. Neither Gly-Gly-beta h-EP nor Arg-beta h-EP antagonized the inhibitory action of beta h-EP or methionine enkephalin. An hour of tissue exposure to 30 nM beta-funaltrexamine followed by thorough washing, displaced to the right, in a parallel fashion, the concentration-response curves of beta h-EP and analogues. Whereas the displacement of the concentration response curves was 8 to 10-fold for beta h-EP and Arg-beta h-EP, it was only about 3-fold for Gly-Gly-beta h-EP and methionine enkephalin. Naltrindole was the most potent antagonist of methionine enkephalin with an apparent pA2 of 9.4; its potency as an antagonist of beta h-EP and related analogues was approximately one-tenth of this with pA2 values approximately 8.5. Norbinaltorphimine also antagonized the action of the opioid peptides with pA2 values close to 7.8.
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lack of mixed agonist antagonist properties of gln8 gly31 βh ep gly gly nh2 and arg9 19 24 28 29 βh ep in the rat vas deferens Neuroeffector Junction studies with naloxone β funaltrexamine and ici 174 864
Journal of Pharmacy and Pharmacology, 2011Co-Authors: R Valenzuela, J P HuidobrotoroAbstract:The 1-27 truncated fragment of beta h-endorphin (beta h-EP) as well as [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 or [Arg9,19,24,28,29]-beta h-EP exhibited opiate agonist activity in the rat vas deferens bioassay; the potency of these peptides was 3 to 6 times less than that of beta h-EP. None of these compounds exhibited any degree of antagonism towards the inhibitory action of beta h-EP. Naloxone antagonized and reversed the inhibitory action of beta h-EP and its analogues though with varying potencies. The apparent naloxone-pA2 value for beta h-EP was 8.94; that for [Gln8-Gly31]-beta h-EP-Gly-Gly-NH2 was 8.08 and that for [Arg9,19,24,28,29]-beta h-EP was 8.38. beta-Funaltrexamine (beta-FNA) potently antagonized the inhibitory action of beta h-EP following non-equilibrium kinetics. Tissue preincubation with 10 nM beta-FNA for 60 min followed by extensive washing caused a 10-fold increase in the beta h-EP IC50. However, 10 nM beta-FNA caused only a 1.2 increase in the IC50 of [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 and a 4.1-fold increase in the IC50 of [Arg9,19,24,28,29]-beta h-EP. In contrast, preincubation of the tissue with 3 microM ICI 174,864 did not modify the potency of beta h-EP or its structural analogues. However, a 60 min pretreatment with 10 microM beta-FNA followed by the addition of 3 microM ICI 174,864 revealed a further decrease in the potency of the opiopeptins compared with tissues exposed to beta-FNA alone or ICI 174,864 alone. In conclusion, the inhibitory action of these peptides is remarkably sensitive to beta-FNA antagonism; in addition the peptides act as pure opiate agonists in marked contrast with the agonist-antagonist properties described in the CNS.
R Valenzuela - One of the best experts on this subject based on the ideXlab platform.
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pharmacological characterization of the inhibitory activity of βh endorphin βh ep arg9 19 24 28 29 βh ep gln8 gly31 βh ep gly gly nh2 in the Neuroeffector Junction of the mouse vas deferens
Journal of Pharmacy and Pharmacology, 2011Co-Authors: R Valenzuela, J P HuidobrotoroAbstract:The inhibitory opioid activities of beta h-endorphin (beta h-EP), its structurally related peptide analogues [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 (Gly-Gly-beta h-EP), [Arg9,19,24,28,29]-beta h-EP (Arg-beta h-EP) and methionine enkephalin have been examined in the electrically stimulated mouse vas deferens bioassay. All four peptides behaved as full agonists; methionine enkephalin was the most potent followed by Arg-beta h-EP, beta h-EP and Gly-Gly-beta h-EP. Neither Gly-Gly-beta h-EP nor Arg-beta h-EP antagonized the inhibitory action of beta h-EP or methionine enkephalin. An hour of tissue exposure to 30 nM beta-funaltrexamine followed by thorough washing, displaced to the right, in a parallel fashion, the concentration-response curves of beta h-EP and analogues. Whereas the displacement of the concentration response curves was 8 to 10-fold for beta h-EP and Arg-beta h-EP, it was only about 3-fold for Gly-Gly-beta h-EP and methionine enkephalin. Naltrindole was the most potent antagonist of methionine enkephalin with an apparent pA2 of 9.4; its potency as an antagonist of beta h-EP and related analogues was approximately one-tenth of this with pA2 values approximately 8.5. Norbinaltorphimine also antagonized the action of the opioid peptides with pA2 values close to 7.8.
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lack of mixed agonist antagonist properties of gln8 gly31 βh ep gly gly nh2 and arg9 19 24 28 29 βh ep in the rat vas deferens Neuroeffector Junction studies with naloxone β funaltrexamine and ici 174 864
Journal of Pharmacy and Pharmacology, 2011Co-Authors: R Valenzuela, J P HuidobrotoroAbstract:The 1-27 truncated fragment of beta h-endorphin (beta h-EP) as well as [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 or [Arg9,19,24,28,29]-beta h-EP exhibited opiate agonist activity in the rat vas deferens bioassay; the potency of these peptides was 3 to 6 times less than that of beta h-EP. None of these compounds exhibited any degree of antagonism towards the inhibitory action of beta h-EP. Naloxone antagonized and reversed the inhibitory action of beta h-EP and its analogues though with varying potencies. The apparent naloxone-pA2 value for beta h-EP was 8.94; that for [Gln8-Gly31]-beta h-EP-Gly-Gly-NH2 was 8.08 and that for [Arg9,19,24,28,29]-beta h-EP was 8.38. beta-Funaltrexamine (beta-FNA) potently antagonized the inhibitory action of beta h-EP following non-equilibrium kinetics. Tissue preincubation with 10 nM beta-FNA for 60 min followed by extensive washing caused a 10-fold increase in the beta h-EP IC50. However, 10 nM beta-FNA caused only a 1.2 increase in the IC50 of [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 and a 4.1-fold increase in the IC50 of [Arg9,19,24,28,29]-beta h-EP. In contrast, preincubation of the tissue with 3 microM ICI 174,864 did not modify the potency of beta h-EP or its structural analogues. However, a 60 min pretreatment with 10 microM beta-FNA followed by the addition of 3 microM ICI 174,864 revealed a further decrease in the potency of the opiopeptins compared with tissues exposed to beta-FNA alone or ICI 174,864 alone. In conclusion, the inhibitory action of these peptides is remarkably sensitive to beta-FNA antagonism; in addition the peptides act as pure opiate agonists in marked contrast with the agonist-antagonist properties described in the CNS.
Diether Lambrechts - One of the best experts on this subject based on the ideXlab platform.
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impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery
Circulation, 2010Co-Authors: Erik Storkebaum, Carmen Ruiz De Almodovar, Merlijn J Meens, Serena Zacchigna, Massimiliano Mazzone, Greet Vanhoutte, Stefan Vinckier, Katarzyna Miskiewicz, Koen Poesen, Diether LambrechtsAbstract:Background— Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular Neuroeffector mechanisms in the adult, however, remain largely unknown. Methods and Results— Here, we report that VEGF∂/∂ mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries. These defects are due to dysfunction and structural remodeling of the Neuroeffector Junction, the equivalent of a synapse between autonomic nerve endings and vascular smooth muscle cells, and to an impaired contractile smooth muscle cell phenotype. Notably, short-term delivery of a VEGF inhibitor to healthy mice also resulted in functional and structural defects of Neuroeffector Junctions. Conclusions— These findings uncover a novel role for VEGF in the maintenance of arterial Neuroeffector function and may help us better understand how VEGF inhibitors cause vascular regulation defects in cance...
Thomas C Cunnane - One of the best experts on this subject based on the ideXlab platform.
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neurotransmitter release mechanisms at the sympathetic Neuroeffector Junction
Experimental Physiology, 1993Co-Authors: James A Brock, Thomas C CunnaneAbstract:CONTENTS PAGE Introduction 591 The quantal hypothesis 592 The vesicular hypothesis 593 Anatomical considerations 593 Intercellular relationships 593 Innervation 594 Sympathetic neurotransmitters 595 Early studies of transmitter release from postganglionic sympathetic nerves 595 Biochemical studies of noradrenaline storage and secretion 596 How much noradrenaline is released from the average varicosity by an action potential? 598 Electrophysiological studies of transmitter release mechanisms at the level of the individual varicosity 598 Intermittent transmitter release 599 ATP as a neurotransmitter at the sympathetic Neuroeffector Junction 601 Why is transmitter release intermittent? 602 Active or passive invasion of nerve terminals by action potentials 605 Biochemistry of depolarization-secretion coupling 606 Chemical modulation of sympathetic neurotransmission 607 Comparison with other neuromuscular Junctions and synapses 609 Concluding remarks 610 References 610
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an electrophysiological study of the actions of angiotensin ii at the sympathetic Neuroeffector Junction in the guinea pig vas deferens
British Journal of Pharmacology, 1991Co-Authors: James Ziogas, Thomas C CunnaneAbstract:1. The effects of angiotensin II on sympathetic Neuroeffector transmission in the guinea-pig vas deferens have been investigated by the use of intracellular and focal extracellular recording techniques to measure indirectly, the release of adenosine 5'-triphosphate (ATP). 2. Angiotensin II (10-100 nM) did not alter the amplitude of the first excitatory Junction potential (e.j.p.) in a train but increased the amplitude of subsequent e.j.ps. There was a corresponding increase in the probability of occurrence of extracellularly recorded evoked excitatory Junction currents (e.j.cs). Spontaneous quantal transmitter release was unaffected by angiotensin II. 3. The enhancement of transmitter release produced by angiotensin II was prevented by the angiotensin receptor antagonist, saralasin. 4. The increase in transmitter release produced by angiotensin II was due to an increase in the probability of transmitter release from individual varicosities and not due to any detectable change in the configuration of the nerve terminal impulse or to the induction of repetitive firing. 5. There was no overall enhancement of e.j.ps or e.j.cs by angiotensin II in reserpinized tissues. Surprisingly, the predominant effect of angiotensin II in reserpinized vasa deferentia was to inhibit evoked transmitter release, an effect reversed by indomethacin (3 microM). 6. The results show that angiotensin II increases the release of sympathetic transmitter by activating preJunctional angiotensin II receptors. However, when the co-transmitter noradrenaline was depleted, angiotensin II now inhibited transmitter release indirectly, presumably by stimulating prostaglandin formation in the smooth muscle cells which then inhibited release transJunctionally.
Erik Storkebaum - One of the best experts on this subject based on the ideXlab platform.
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Molecular Cardiology Impaired Autonomic Regulation of Resistance Arteries in Mice With Low Vascular Endothelial Growth Factor or Upon Vascular Endothelial Growth Factor Trap Delivery
2016Co-Authors: Erik Storkebaum, Serena Zacchigna, Ruiz Almodovar, Phd* Merlijn Meens, Phd Massimiliano Mazzone, Phd Greet Vanhoutte, Jo G. R, De Mey, Phd Peter CarmelietAbstract:Background—Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular Neuroeffector mechanisms in the adult, however, remain largely unknown. Methods and Results—Here, we report that VEGF/ mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries. These defects are due to dysfunction and structural remodeling of the Neuroeffector Junction, the equivalent of a synapse between autonomic nerve endings and vascular smooth muscle cells, and to an impaired contractile smooth muscle cell phenotype. Notably, short-term delivery of a VEGF inhibitor to healthy mice also resulted in functional and structural defects of Neuroeffector Junctions. Conclusions—These findings uncover a novel role for VEGF in the maintenance of arterial Neuroeffector function and may help us better understand how VEGF inhibitors cause vascular regulation defects in cancer patients. (Circulation. 2010;122:273-281.) Key Words: arteries muscle, smooth nervous system vascular endothelial growth factor vasoconstriction Several cues have been identified that control the devel-opment of the sympathetic nervous system,1 but the molecular mechanisms underlying the maintenance of auto-nomic innervation of peripheral resistance arteries in adult-hood remain largely unknown. Periarterial nerves do not penetrate the medial vascular smooth muscle cell (SMC
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impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery
Circulation, 2010Co-Authors: Erik Storkebaum, Carmen Ruiz De Almodovar, Merlijn J Meens, Serena Zacchigna, Massimiliano Mazzone, Greet Vanhoutte, Stefan Vinckier, Katarzyna Miskiewicz, Koen Poesen, Diether LambrechtsAbstract:Background— Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular Neuroeffector mechanisms in the adult, however, remain largely unknown. Methods and Results— Here, we report that VEGF∂/∂ mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries. These defects are due to dysfunction and structural remodeling of the Neuroeffector Junction, the equivalent of a synapse between autonomic nerve endings and vascular smooth muscle cells, and to an impaired contractile smooth muscle cell phenotype. Notably, short-term delivery of a VEGF inhibitor to healthy mice also resulted in functional and structural defects of Neuroeffector Junctions. Conclusions— These findings uncover a novel role for VEGF in the maintenance of arterial Neuroeffector function and may help us better understand how VEGF inhibitors cause vascular regulation defects in cance...