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 induced contraction of prostate strips from the peripheral zone, (‘the capsule’). Bethanechol contracted the tissue but not at lower doses. McN-A-343 and oxotremorine-M showed the same effects. 3 Blocking α- and β-adrenoceptors with phentolamine and propranolol, respectively, did not modify carbachol-induced contractions. 4 The nicotinic receptor blocker, hexamethonium (10^??6–10^??4 m ) did not affect the contractile response evoked by a single dose of carbachol (10^??5 m ), whilst the muscarinic receptor antagonist, atropine (10^??11–10^??9 m ), inhibited it in a competitive manner. 5 The muscarinic M₁ (pirenzepine), M₂AF-DX 116, himbacine (M₂/M₄) and methoctramine], M₃ (HHSID and f-F-HHSID), and putative M₄ (tropicamide) antagonists reduced significantly the carbachol-induced contractions. The pIC₅₀ values were: atropine (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 M₂ receptor subtype could mediate the muscarinic contraction in the canine prostate.