The Guinea Pig Ileum Lacks the Direct, High-Potency, M2-Muscarinic, Contractile Mechanism of the Mouse Ileum

Authors

Michael T. Griffin, Chapman UniversityFollow
Minoru Matsui, Chiba Institute of Science
Rennolds S. Ostrom, Chapman UniversityFollow
Frederick J. Ehlert, University of California, Irvine

Document Type

Article

Publication Date

2009

Abstract

We explored whether the M2 muscarinic receptor in the guinea pig ileum elicits a highly potent, direct-contractile response, like that from the M3 muscarinic receptor knockout mouse. First, we characterized the irreversible receptor-blocking activity of 4-DAMP mustard in ileum from muscarinic receptor knockout mice to verify its M3 selectivity. Then, we used 4-DAMP mustard to inactivate M3 responses in the guinea pig ileum to attempt to reveal direct, M2 receptor-mediated contractions. The muscarinic agonist, oxotremorine-M, elicited potent contractions in ileum from wild-type, M2 receptor knockout, and M3 receptor knockout mice characterized by negative log EC50 (pEC50) values ± SEM of 6.75 ± 0.03, 6.26 ± 0.05, and 6.99 ± 0.08, respectively. The corresponding Emax values in wild-type and M2 receptor knockout mice were approximately the same, but that in the M3 receptor knockout mouse was only 36% of wild type. Following 4-DAMP mustard treatment, the concentration–response curve of oxotremorine-M in wild-type ileum resembled that of the M3 knockout mouse in terms of its pEC50, Emax, and inhibition by selective muscarinic antagonists. Thus, 4-DAMP mustard treatment appears to inactivate M3 responses selectively and renders the muscarinic contractile behavior of the wild-type ileum similar to that of the M3 knockout mouse. Following 4-DAMP mustard treatment, the contractile response of the guinea pig ileum to oxotremorine-M exhibited low potency and a competitive-antagonism profile consistent with an M3 response. The guinea pig ileum, therefore, lacks a direct, highly potent, M2-contractile component but may have a direct, lower potency M2 component.

Comments

This article was originally published in Naunyn-Schmiedeberg's Archives of Pharmacology, volume 380, issue 4, in 2009. DOI: 10.1007/s00210-009-0434-8

Recommended Citation

Michael T. Griffin, Minoru Matsui, Rennolds S Ostrom and Frederick J. Ehlert. The guinea pig ileum lacks the direct, high-potency, M2-muscarinic, contractile mechanism of the mouse ileum. Naunyn-Schmiedebergs Arch Pharmacol, 380(4):327-35, 2009

Copyright

The authors