title: Differential coupling of muscarinic M1, M2, and M3 receptors to phosphoinositide hydrolysis in urinary bladder and longitudinal muscle of the ileum of the mouse.
abstract: We investigated the coupling of muscarinic receptor (M) subtypes to phosphoinositide hydrolysis in ileum and urinary bladder using muscarinic receptor knockout mice. In urinary bladder from wild-type mice, the muscarinic agonist oxotremorine-M, elicited a robust phosphoinositide response characterized by an EC50 value of 0.22 microM and a maximal response (Emax) of 32.8% conversion of [3H]inositol-labeled phosphoinositides into [3H]inositol phosphates. A similar response was observed in urinary bladder from M2 knockout mice, whereas no measurable response was observed in urinary bladder from M3 and M2/M3 knockout mice. In ilea from wild-type and M2 knockout mice, substantial phosphoinositide responses to oxotremorine-M were measured, characterized by EC50 values of 0.37 and 0.52 microM and Emax values of 35.8 and 34.7%, respectively. Oxotremorine-M also elicited phosphoinositide hydrolysis in ilea from M3 and M2/M3 knockout mice, although these responses were less sensitive (EC50 values of 1.6 and 1.4 microM; Emax values of 31.2 and 20.8%, respectively). The response in ileum from the M2/M3 knockout was significantly smaller than that from the M3 knockout. The muscarinic phosphoinositide response in ilea from M2/M3 knockout mice originated in the smooth muscle and exhibited a profile for competitive antagonism consistent with an M1 mechanism. These data suggest a major role for the M3 receptor in eliciting phosphoinositide hydrolysis in the ileum and urinary bladder and minor roles for the M1 and M2 in ileum.
authors: Department of Pharmacology, College of Medicine, University of California, Irvine, CA 92697-4625, USA.
authors: John A
authors: JA
authors: Tran
authors: Minoru
authors: M
authors: Matsui
authors: Frederick J
authors: FJ
authors: Ehlert