On the functional role of muscarinic M-2 receptors in cholinergic and purinergic responses in the rat urinary bladder

The functional effects of muscarinic receptor and purinoceptor agonists and antagonists were studied on isolated strip preparations of the rat urinary bladder. The muscarinic "M-3/M-1-selective" receptor antagonist 4-diphenyl acetoxy-N-methylpiperidine methobromide (4-DAMP) most conspicuously inhibit ed the carbachol-evoked contractile responses (p A(2) = 9.8). while the mus carinic "M-1-selective" receptor antagonist pirenzepine and the muscarinic "M-2-selective" receptor antagonist methoctramine were less potent (pA(2) = 7.0 and 6.5, respectively). Administration of 4-DAMP in combination with m ethoctramine 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 relax ation of the carbachol-contracted detrusor strips. The relaxatory response was enhanced in the presence of methoctramine and furthermore, was attenuat ed by the adenosine receptor antagonist 8-p-sulfophenyltheophylline. Admini stration of 2-chloro-adenosine to pre-contracted strips tended to cause dos e-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 th e cholinergic contractile response in the rat urinary bladder being exerted via activation of muscarinic M-3 receptors, while the muscarinic M-3 recep tors exerted a modulator effect on purine-evoked relaxations in the rat uri nary bladder. (C) 2001 Elsevier Science BN. All rights reserved.