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Interaction between muscarinic receptor subtype signal transduction pathways mediating bladder contraction.

Authors: Braverman, AS  Tallarida, RJ  Ruggieri MR, SR 
Citation: Braverman AS, etal., Am J Physiol Regul Integr Comp Physiol 2002 Sep;283(3):R663-8.
Pubmed: (View Article at PubMed) PMID:12185001
DOI: Full-text: DOI:10.1152/ajpregu.00116.2002

M(3) muscarinic receptors mediate cholinergic-induced contraction in most smooth muscles. However, in the denervated rat bladder, M(2) receptors participate in contraction because M(3)-selective antagonists [para-fluoro-hexahydro-sila-diphenidol (p-F-HHSiD) and 4-DAMP] have low affinities. However, the affinity of the M(2)-selective antagonist methoctramine in the denervated bladder is consistent with M(3) receptor mediating contraction. It is possible that two pathways interact to mediate contraction: one mediated by the M(2) receptor and one by the M(3) receptor. To determine whether an interaction exists, the inhibitory potencies of combinations of methoctramine and p-F-HHSiD for reversing cholinergic contractions were measured. In normal bladders, all combinations gave additive effects. In denervated bladders, synergistic effects were seen with the 10:1 and 1:1 (methoctramine:p-F-HHSiD wt/wt) combinations. After application of the sarcoplasmic reticulum ATPase inhibitor thapsigargin to normal tissue, the 10:1 and 1:1 ratios became synergistic, mimicking denervated tissue. Thus in normal bladders both M(2) and M(3) receptors can induce contraction. In the denervated bladder, the M(2) and the M(3) receptors interact in a facilitatory manner to mediate contraction.


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CRRD Object Information
CRRD ID: 724728
Created: 2003-10-20
Species: All species
Last Modified: 2003-10-20
Status: ACTIVE


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