| Heterogeneity of presynaptic muscarinic receptors mediating inhibition of sympathetic transmitter release: a study with M2- and M4-receptor-deficient mice. | |
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MedLine Citation:
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PMID: 12569072 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1 Presynaptic muscarinic receptors modulate sympathetic transmitter release. The goal of the present study was to identify the muscarinic receptor subtype(s) mediating inhibition of sympathetic transmitter release in mouse atria, urinary bladder and vas deferens. To address this question, electrically evoked noradrenaline release was assessed using tissue preparations from NMRI, M(2)- and M(4)-knockout, and the corresponding M(2)- and M(4)-wildtype mice, after preincubation with (3)H-noradrenaline. 2 The muscarinic agonist carbachol decreased evoked tritium overflow (20 pulses/50 Hz) in each tissue and strain investigated. After deletion of the M(2)-receptor the maximal inhibition by carbachol was significantly reduced (by 41-72%), but not abolished, in all tissues. After deletion of the M(4)-receptor a moderate and significant reduction of the maximal inhibition by carbachol (by 28%) was observed only in the vas deferens. 3 Experiments with the muscarinic antagonists methoctramine and pirenzepine confirmed that the presynaptic muscarinic receptors were predominantly M(2) in atria and bladder and probably a mixture of M(2) and M(4) in the vas deferens. 4 Experiments in the urinary bladder with the cholinesterase inhibitor physostigmine and the muscarinic antagonist ipratropium demonstrated that endogenously released acetylcholine predominantly acted through M(2)-receptors to inhibit noradrenaline release. However, the results do not exclude a minor contribution of M(4)-receptors to this endogenous inhibition. 5 In conclusion, our results clearly indicate that the release-inhibiting muscarinic receptors on postganglionic sympathetic axons in mouse atria, bladder and vas deferens represent mixtures of M(2)- and non-M(2)-receptors. The non-M(2)-receptors remain unknown in atria and the bladder, and may represent primarily M(4)-receptors in the vas deferens. These results reveal an unexpected heterogeneity among the muscarinic receptors mediating inhibition of noradrenaline release. |
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Authors:
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Anne-Ulrike Trendelenburg; Jesus Gomeza; Werner Klebroff; Hongxia Zhou; Jürgen Wess |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 138 ISSN: 0007-1188 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2003 Feb |
Date Detail:
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Created Date: 2003-02-05 Completed Date: 2003-10-14 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 469-80 Citation Subset: IM |
Affiliation:
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Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albertstrasse 25, D-79104 Freiburg, Germany. anne-ulrike.trendelenburg@pharma.novartis.com |
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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antagonists & inhibitors*,
metabolism Animals Carbachol / pharmacology Cholinergic Agonists / pharmacology Diamines / pharmacology Genetic Heterogeneity* Heart Atria / drug effects, metabolism Male Mice Mice, Knockout Muscarinic Antagonists / pharmacology Norepinephrine / metabolism* Pirenzepine / pharmacology Receptor, Muscarinic M2 Receptor, Muscarinic M4 Receptors, Muscarinic / drug effects, genetics, physiology* Receptors, Presynaptic / drug effects, genetics, physiology* Urinary Bladder / drug effects, metabolism Vas Deferens / drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cholinergic Agonists; 0/Diamines; 0/Muscarinic Antagonists; 0/Receptor, Muscarinic M2; 0/Receptor, Muscarinic M4; 0/Receptors, Muscarinic; 0/Receptors, Presynaptic; 104807-46-7/methoctramine; 28797-61-7/Pirenzepine; 51-41-2/Norepinephrine; 51-83-2/Carbachol; 51-84-3/Acetylcholine |
| Comments/Corrections | |
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