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On the functional role of muscarinic M2 receptors in cholinergic and purinergic responses in the rat urinary bladder.

Journal article
Authors Daniel Giglio
Dick Delbro
Gunnar Tobin
Published in European journal of pharmacology
Volume 428
Issue 3
Pages 357-64
ISSN 0014-2999
Publication year 2001
Published at Institute of Physiology and Pharmacology, Dept of Pharmacology
Institute of Surgical Sciences, Department of Surgery
Pages 357-64
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords 2-Chloroadenosine, pharmacology, Adenosine, pharmacology, Adenosine Triphosphate, pharmacology, Animals, Carbachol, pharmacology, Diamines, pharmacology, Dose-Response Relationship, Drug, Male, Muscarinic Agonists, pharmacology, Muscarinic Antagonists, pharmacology, Muscle Contraction, drug effects, Piperidines, pharmacology, Pirenzepine, pharmacology, Rats, Rats, Sprague-Dawley, Receptor, Muscarinic M2, Receptors, Muscarinic, drug effects, physiology, Receptors, Purinergic, agonists, antagonists & inhibitors, physiology, Theophylline, analogs & derivatives, pharmacology, Urinary Bladder, drug effects, physiology
Subject categories Pharmacology

Abstract

The functional effects of muscarinic receptor and purinoceptor agonists and antagonists were studied on isolated strip preparations of the rat urinary bladder. The muscarinic "M3/M1-selective" receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP) most conspicuously inhibited the carbachol-evoked contractile responses (pA2=9.8), while the muscarinic "M1-selective" receptor antagonist pirenzepine and the muscarinic "M2-selective" receptor antagonist methoctramine were less potent (pA2=7.0 and 6.5, respectively). Administration of 4-DAMP in combination with methoctramine in selective dosages gave no significant additional reduction of carbachol-evoked contractile responses. Adenosine 5'-triphosphate (ATP) elicited transient dose-dependent contractile responses and it caused relaxation of the carbachol-contracted detrusor strips. The relaxatory response was enhanced in the presence of methoctramine and furthermore, was attenuated by the adenosine receptor antagonist 8-p-sulfophenyltheophylline. Administration of 2-chloro-adenosine to pre-contracted strips tended to cause dose-dependent relaxations, which were significantly increased in the presence of methoctramine. The purinergic contractile response, on the other hand, was not affected by methoctramine. Thus, the results are consistent with the cholinergic contractile response in the rat urinary bladder being exerted via activation of muscarinic M3 receptors, while the muscarinic M2 receptors exerted a modulator effect on purine-evoked relaxations in the rat urinary bladder.

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