Prostanoid synthesis by the rat urinary bladder: evidence for stimulation through muscarine receptor-linked calcium channels

Summary

An in vitro model for the study of muscarine receptor-mediated synthesis of prostacyclin (PGI₂) and other prostanoids (PGE₂ and PGF_2α ) by the rat urinary bladder is described. PGI₂ synthesis was stimulated by parasympathomimetic agents (carbachol > methacholine > arecoline; McNA 343, nicotine and dimethyl phenyl piperazinium were without effect). Methacholine (3×10⁻⁶ mol·l⁻¹)-stimulated PGI₂ synthesis was inhibited by muscarinic antagonists (atropine > ipratroprium bromide > gallamine > pirenzepine) and was completely abolished by the presence of ethylene diamine tetraacetic acid (EDTA: 10 mmol·l⁻¹). Verapamil also inhibited methacholine-stimulated PGI₂ synthesis in a dose-dependent manner. The antagonistic action of atropine was shown to be competitive, but had no effect on calcium ionophore A23187-stimulated PGI₂ synthesis. High concentrations of [K⁺] (up to 0.11 mol·l⁻¹) were without effect on PGI₂ synthesis. PGE₂, PGF_2α and PGI₂ synthesis were all equally stimulated with methacholine, carbachol, arecoline and A23187, and methacholine-stimulated synthesis of these prostanoids was equally inhibited by atropine, ipratroprium bromide, gallamine, verapamil and EDTA.

It is concluded that in vitro prostanoid synthesis by the rat urinary bladder: (i) is stimulated by post ganglionic muscarine receptors; (ii) involves a muscarine receptorlinked calcium influx system; and (iii) is mediated by a predominance of M₂ subtype receptors.