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

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Braverman AS, Tallarida RJ, Ruggieri MR Sr

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

Am J Physiol Regul Integr Comp Physiol. 2002 Sep;283(3):R663-8.

PubMed ID

12185001 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Diphenidol	Muscarinic acetylcholine receptor M2	Protein	Humans	Yes	Antagonist	Details
Diphenidol	Muscarinic acetylcholine receptor M3	Protein	Humans	Yes	Antagonist	Details