Are m-Cholinoceptors of Guinea Pig Gallbladder Smooth Muscle of m₄ Subtype?

Abstract

The antagonism of carbachol-induced contractions of guinea pig gallbladder smooth muscle strips via selective antagonists, methoctramine, HHSiD, pf-HHSiD and DABDMA has been investigated in order to find out the m-cholinoceptor subtype(s) of gallbladder smooth muscle. All m-cholinoceptor antagonists examined, displaced the concentration-response curves to the right parallel in a concentration-dependent manner without affecting the maximum response. Schild analysis of data was consistent with competitive antagonism, –log K_B values of the antagonists were 7.37 for HHSiD, 7.53 for pf-HHSiD, 6.58 for DABDMA and 7.60 for methoctramine. These results, together with the high affinity of pirenzepine and low affinities of 4-DAMP and AF-DX 116, indicate that the m-cholinoceptors of the guinea pig gallbladder which mediate cholinergic contractions are not of m₁-, m₂- and m₃-subtypes but seem likely to be of m₄-subtype.

Muscarinic Receptor Knockout Mice: Role of Muscarinic Acetylcholine Receptors M2, M3, and M4 in Carbamylcholine-Induced Gallbladder Contractility

“…The gallbladder was a uniquely interesting smooth muscle based on the proposed presence of M 4 receptors and their role in mediating smooth muscle contractility (Ozkutlu et al, 1993;Karaalp et al, 1999;Akici et al, 2000). Carbamylcholine-induced contraction in gallbladder from M 4 receptor knockout mice was dextrally shifted compared with the response in gallbladder from wild-type mice, suggesting that the M 4 receptor participated in the contraction to carbamylcholine.…”

“…The possibility of a prominent role for M 3 and a more modest role for M 2 receptors in muscarinic-induced contraction of gallbladder is consistent with previous observations documenting a similar role for these receptors in carbamylcholine-induced contraction of other smooth muscles such as mouse trachea, stomach fundus, and urinary bladder (Stengel et al, 2000). In addition to these muscarinic receptors, the M 4 receptor has also been proposed to play an important role in contractility of the guinea pig gallbladder (Ozkutlu et al, 1993;Karaalp et al, 1999;Akici et al, 2000). The possibility that M 4 receptors may be involved in gallbladder contraction deserves careful consideration because it markedly contrasts with the lack of M 4 receptor involvement in the contraction of other smooth muscle preparations (Stengel et al, 2000).…”

Distribution and function of the muscarinic receptor subtypes in the cardiovascular system

“…Evidence acquired from canine atrial tissue suggests a potential role for AChM4R in the control of K ϩ channels (11,95). AChM4R has been shown to be involved in the contractile responses of smooth muscle in the uterus and gall bladder, suggesting that it may have a role in contractile responses in other smooth muscle tissues, but more evidence is needed (27,85,86). A recent study using muscarinic KO mice suggested that AChM4R receptors may also play a minor role in facilitating AChM2R receptor-mediated bradycardia, but further studies are warranted to elucidate what role, if any, AChM4R plays in the cardiovascular system (98).…”