Muscarinic receptors mediating contraction of female mouse urinary bladder: effects of oestrogen.

Muscarinic receptors mediating contraction of bladder detrusor muscle from female mice were examined. Mice were untreated (A) or treated with oestradiol cypionate (200 microg/kg) 24 h (B) or 96 h (C) before experimentation, or were pregnant (day 17) (D). Saturation radioligand binding experiments using [(3)H]quinuclidinyl benzilate ([(3)H] QNB) indicated similar muscarinic receptor densities and affinities in bladders from groups A and B. Neither oestrogen treatment nor pregnancy altered pD(2) estimates for methacholine. Maximum responses to methacholine and high-K(+) physiological salt solution (KPSS) were significantly greater (P<0.05) in tissues from groups C and D than in A and B. Potencies of other muscarinic receptor agonists were similar in groups A and B with an order of acetylcholine plus physostigmine (10 microM) approximately methacholine plus physostigmine (10 microM)>methacholine approximately acetylcholine>bethanechol. Antagonist pK(B) estimates were similar in bladders from groups A and B with a rank order of: atropine>/=4-diphenyl acetoxy-N-methyl piperidine methiodide>parafluorohexahydrosiladifenidol approximately pirenzepine>himbacine, implicating muscarinic M(1) and/or M(5) as well as muscarinic M(3) receptors in mediating methacholine-induced bladder contraction.