Characterisation of the prejunctional inhibitory muscarinic receptor on cholinergic nerves in the rat urinary bladder

The nature of the prejunctional inhibitory muscarinic receptor on cholinerg ic nerve endings in the rat urinary bladder was investigated by measuring s timulated endogenous acetylcholine release via high pressure liquid chromat ography (HPLC), in the presence of various selective muscarinic antagonists . The rank order of potencies for the antagonists used was: atropine (-log concentration = 7.8) > 4-DAMP (4-diphenylacetoxy-N-methylpiperidine) (7.6) > tripitramine (7.3) = HHD (hexahydrodifenidol) (7.3) > pFHHSiD (p-fluorohe xahydrosiladifenidol hydrochloride) (7.0) > himbacine (6.5) > methoctramine (5.9) greater than or equal to pirenzepine (5.8) > gallamine (4.3). A comp arison of the antagonist potencies obtained, with affinity constants at mus carinic M-1 to M-5 receptors, suggests that the prejunctional inhibitory mu scarinic receptor is of the M-4 receptor subtype. (C) 2001 Published by Els evier Science B.V.