ARE M-CHOLINOCEPTORS OF GUINEA-PIG GALLBLADDER SMOOTH-MUSCLE OF M4 SUBTYPE

The antagonism of carbachol-induced contractions of guinea pig gallbla dder smooth muscle strips via selective antagonists, methoctramine, HH SiD, pf-HHSiD and DABDMA has been investigated in order to find out th e m-cholinoceptor subtype(s) of gallbladder smooth muscle. All m-choli noceptor antagonists examined, displaced the concentration-response cu rves to the right parallel in a concentration-dependent manner without affecting the maximum response. Schild analysis of data was consisten t with competitive antagonism. -log K(B) values of the antagonists wer e 7.37 for HHSiD, 7.53 for pf-HHSiD, 6.58 for DABDMA and 7.60 for meth octramine. These results, together with the high affinity of pirenzepi ne and low affinities of 4-DAMP and AF-DX 116, indicate that the m-cho linoceptors of the guinea pig gallbladder which mediate cholinergic co ntractions are not of m1-, m2- and m3-subtypes but seem likely to be o f m4-subtype.