Promiscuous or heterogeneous muscarinic receptors in rat atria? II. Antagonism of responses to carbachol by pirenzepine

European Journal of Pharmacology
C Boselli, T P Kenakin

Abstract

Carbachol produces both negative and positive inotropy in rat left atria. It is not clear whether these two effects are mediated by two separate cell surface muscarinic receptors or a single receptor interacting with two coupling proteins in the cell membrane. Pirenzepine, known to selectively block some biochemical muscarinic responses, was used in this study to block the biphasic response to carbachol in rat left atria. The negative inotropy to carbachol was blocked by pirenzepine, and Schild analysis indicated a -log dissociation constant (pKb) for the pirenzepine-receptor complex of 6.2. However, the Schild analysis may have been complicated by positive inotropy observed with pirenzepine. This positive inotropic effect was sensitive to blockade by other muscarinic antagonists. In atria from rats pretreated with pertussis toxin, carbachol produced a positive inotropic effect. Schild analysis with pirenzepine for antagonism of this response indicated a -log equilibrium dissociation constant for the pirenzepine-receptor complex of 6.7, significantly different from that for antagonism of negative inotropy. This ostensibly suggested a difference in the receptors mediating these responses. In view of the possible complicating eff...Continue Reading

References

Nov 1, 1986·British Journal of Pharmacology·J W BlackN P Shankley
Jan 1, 1989·Trends in Pharmacological Sciences·T P Kenakin
Mar 1, 1959·British Journal of Pharmacology and Chemotherapy·O ARUNLAKSHANA, H O SCHILD
Jan 21, 2010·Journal of Biomolecular Screening·Terry P Kenakin
Feb 16, 2013·Current Topics in Medicinal Chemistry·Terry Kenakin

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Citations

Aug 1, 1991·Naunyn-Schmiedeberg's Archives of Pharmacology·T P Kenakin, C Boselli
Nov 11, 1999·European Journal of Pharmacology·A ChristopoulosE E El-Fakahany
Aug 1, 1994·Journal of Autonomic Pharmacology·N Watson, R M Eglen

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