Evaluation of mRNAs Encoding Muscarinic Receptor Subtypes in Human Detrusor Muscle

Abstract

These results suggest that human detrusor muscle coexpresses muscarinic m2 and m3 receptors and that the populations of the 2 subtypes are not significantly different.

The role of M2‐muscarinic receptors in mediating contraction of the pig urinary bladder in vitro

“…The present study investigated whether an M 2 -mediated response could be demonstrated in the pig bladder where the M 2 : M 3 ratio is lower than that found in the rat. The M 2 : M 3 ratio of 3 : 1 obtained in the present study is signi®cantly lower than that found in the rat, but is similar to the value recorded for the human bladder (Wang et al, 1995;Yamaguchi et al, 1996).…”

“…Hill slopes for all three antagonists were low, which supports the concept of two-site binding and this was further supported in tissues following M 3 -alkylation, where only one binding site (M 2 ) could be observed. The radioligand binding data therefore demonstrated a minority M 3 -receptor population of about 25% in the pig bladder, and this ratio is similar to that reported previously for the human bladder (Wang et al, 1995;Yamaguchi et al, 1996). For this reason we investigated the receptor subtype mediating functional responses in this species.…”

Functional Selectivity of Muscarinic Receptor Antagonists for Inhibition of M3-Mediated Phosphoinositide Responses in Guinea Pig Urinary Bladder and Submandibular Salivary Gland

“…Molecular techniques have identified five muscarinic acetylcholine (mACh) receptor subtypes (m1-m5), whereas pharmacological data can distinguish only four subtypes, denoted as M 1 to M 4 (Caulfield and Birdsall, 1998). Both M 2 and M 3 mACh receptors have been identified in bladder (detrusor) smooth muscle at the level of mRNA (Yamaguchi et al, 1996) and protein, with quantitative immunoprecipitation demonstrating a 75 to 90% predominance of the M 2 subtype in all species studied (Wang et al, 1995). Roles for the majority M 2 receptor population in the contraction of various smooth muscle types (including bladder detrusor) have been proposed, based upon observations in tissues treated with N-2-chloroethyl-4-piperidinyl diphenylacetate selectively to inactivate the M 3 receptor population.…”

This article has been retracted

“…18,19,21 In human bladder smooth muscles, mRNAs encoding M 2 and M 3 subtypes have been detected. 20 The population of muscarinic M 2 and M 3 receptors is approximately 9 : 1 in the rat bladder and approximately 3 : 1 in all other species. 38 Despite the dominant presence of M 2 receptors, functional studies using several anticholinergic drugs indicate M 3 receptors mainly mediate bladder smooth muscle contractions.…”

“…18,19 The muscarinic receptors found in the detrusor are of the M 2 and M 3 subtypes. 20 Despite the dominant presence of the M 2 receptor, functional studies using several anticholinergic drugs indicate that M 3 receptors are mainly responsible for the normal micturition contraction. 21,22 Therefore, in the present study, on the hypothesis that an overexpression of M 3 receptor may enhance the smooth muscle contractility or the responsiveness to the muscarinic agent, we attempted to transfer M 3 genes into the rat urinary bladder using an in vivo EP procedure.…”