Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 334, Issue 4, pp 463–467

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

  • J. Y. Jeremy
  • D. P. Mikhailidis
  • P. Dandona
Article

Summary

An in vitro model for the study of muscarine receptor-mediated synthesis of prostacyclin (PGI2) and other prostanoids (PGE2 and PGF2α) 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, PGF2α 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.

Key words

Urinary bladder Prostacyclin Prostaglandin E2 Prostaglandin F2α Muscarine receptors 

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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • J. Y. Jeremy
    • 1
  • D. P. Mikhailidis
    • 1
  • P. Dandona
    • 1
  1. 1.Metabolic Unit, Department of Chemical Pathology and Human MetabolismRoyal Free Hospital and School of MedicineLondonUK

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