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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-3-18
pubmed:abstractText
We investigated the contractile role of M2 muscarinic receptors in mouse urinary bladder. When measured in the absence of other agents, contractions elicited to the muscarinic agonist oxotremorine-M exhibited properties consistent with that expected for an M3 response in urinary bladder from wild-type and M2 knockout (KO) mice. Evidence for a minor M2 receptor-mediated contraction was revealed by a comparison of responses in M3 knockout and M2/M3 double knockout mice. Treatment of wild-type and M2 knockout urinary bladder with N-2-chloroethyl-4-piperidinyl diphenylacetate (4-DAMP mustard) caused a large inhibition of the muscarinic contractile response. The residual contractions were much smaller in M2 knockout bladder compared with wild type, suggesting that M2 receptors rescue the muscarinic contractile response in wild-type bladder following inactivation of M3 receptors with 4-DAMP mustard. When measured in the presence of prostaglandin F2alpha and isoproterenol or forskolin, oxotremorine-M mediated a potent contractile response in urinary bladder from M3 KO mice. This response exhibited an M2 profile in competitive antagonism studies and was completely absent in M2/M3 KO mice. Following 4-DAMP mustard treatment, oxotremorine-M elicited a contractile response in wild-type urinary bladder in the presence of KCl and isoproterenol or forskolin, and this response was diminished in M2 KO mice. Our results show that the M2 receptor mediates contractions indirectly in the urinary bladder by enhancing M3 receptor-mediated contractions and inhibiting relaxation. We also show that it is difficult to detect M2 receptor function in competitive antagonism studies under conditions where a simultaneous activation of M2 and M3 receptors occurs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
313
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
368-78
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15608083-Adrenergic beta-Agonists, pubmed-meshheading:15608083-Animals, pubmed-meshheading:15608083-Binding, Competitive, pubmed-meshheading:15608083-Dinoprost, pubmed-meshheading:15608083-Diphenylacetic Acids, pubmed-meshheading:15608083-Forskolin, pubmed-meshheading:15608083-Isoproterenol, pubmed-meshheading:15608083-Mice, pubmed-meshheading:15608083-Mice, Inbred C57BL, pubmed-meshheading:15608083-Mice, Knockout, pubmed-meshheading:15608083-Muscarinic Agonists, pubmed-meshheading:15608083-Muscle, Smooth, pubmed-meshheading:15608083-Muscle Contraction, pubmed-meshheading:15608083-Muscle Relaxation, pubmed-meshheading:15608083-Oxotremorine, pubmed-meshheading:15608083-Piperidines, pubmed-meshheading:15608083-Receptor, Muscarinic M2, pubmed-meshheading:15608083-Receptor, Muscarinic M3, pubmed-meshheading:15608083-Urinary Bladder
pubmed:year
2005
pubmed:articleTitle
The M2 muscarinic receptor mediates contraction through indirect mechanisms in mouse urinary bladder.
pubmed:affiliation
Department of Pharmacology, College of Medicine, University of California Irvine, Irvine, CA 92697-4625, USA. fjehlert@uci.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't