CHARACTERIZATION OF THE MUSCARINIC RECEPTOR MEDIATING CONTRACTION OF THE DOG PROSTATE

1 We have studied the effects of muscarinic cholinoceptor agonists and subtype-preferring antagonists on the isometric contraction of smooth muscle strips from dog prostate. 2 Acetylcholine and carbachol induce d contraction of prostate strips from the peripheral zone, ('the capsu le'). Bethanechol contracted the tissue but not at lower doses. McN-A- 343 and oxotremorine-M showed the same effects. 3 Blocking alpha- and beta-adrenoceptors with phentolamine and propranolol, respectively, di d not modify carbachol-induced contractions. 4 The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M) did not affect the contractil e response evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic receptor antagonist, atropine (10(-11)-10(-9) M), inhibite d it in a competitive manner. 5 The muscarinic M-1 (pirenzepine), M-2 [AF-DX 116, himbacine (M-2/M-4) and methoctramine], M-3 (HHSID and f-F -HHSID), and putative M-4 (tropicamide) antagonists reduced significan tly the carbachol-induced contractions. The pIC(50) values were: atrop ine (10.01) > himbacine (8.3) > methoctramine (7.85) > AF-DX 116 (7.60 ) > HHSID (7.21) > p-F-HHSID (7.10) > pirenzepine (7.30) > tropicamide (7.00). 6 The antagonist profile indicates that an predominant M-2 re ceptor subtype could mediate the muscarinic contraction in the canine prostate.