MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brown, J. H.
Right arrow Articles by Masters, S. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brown, J. H.
Right arrow Articles by Masters, S. B.

The putative M1 muscarinic receptor does not regulate phosphoinositide hydrolysis. Studies with pirenzepine and McN-A343 in chick heart and astrocytoma cells

JH Brown, D Goldstein and SB Masters

Muscarinic receptor activation stimulates phosphoinositide hydrolysis and inhibits cyclic AMP formation in dissociated embryonic chick heart cells. We used this preparation to examine the hypothesis that the putative M1 and M2 receptor subtypes are selectively coupled to these two responses. Atropine blocks the effects of carbachol on cyclic AMP formation and phosphoinositide breakdown with nearly identical KI values (1.9 and 0.8 nM); these values are close to the apparent KD (1.8 nM) of atropine competition for [3H]N-methylscopolamine binding. Pirenzepine blocks the effect of carbachol on cyclic AMP formation with a KI of 48 nM, a value similar to the apparent KD (23 nM) determined in radioligand-binding studies. In contrast, a higher concentration of pirenzepine is needed to inhibit carbachol-stimulated phosphoinositide hydrolysis (KI = 255 nM). Two selective agonists, McN-A343 and AHR 602, inhibit cyclic AMP formation but do not stimulate phosphoinositide hydrolysis in chick heart cells. Muscarinic receptor-mediated phosphoinositide hydrolysis in 1321N1 astrocytoma cells is also insensitive to McN-A343 or AHR 602 and is antagonized only by relatively high concentrations of pirenzepine. The M1 receptor, as previously defined, has high affinity for pirenzepine and is activated by McN-A343. We find that these ligands have greater activity at muscarinic receptors that inhibit cyclic AMP formation than at those that stimulate phosphoinositide hydrolysis. Thus, if different receptor subtypes are associated with these two responses, the M1 receptor regulates cyclic AMP rather than phosphoinositide metabolism. Our data also demonstrate that the chick heart has muscarinic receptors with high affinity for pirenzepine, and thus, in contrast to rat heart, appears to have predominantly M1 receptors.

Volume 27, Issue 5, pp. 525-531, 05/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
L. A. McKinnon and N. M. Nathanson
Tissue-specific Regulation of Muscarinic Acetylcholine Receptor Expression during Embryonic Development
J. Biol. Chem., September 1, 1995; 270(35): 20636 - 20642.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A Ashkenazi, J. Winslow, E. Peralta, G. Peterson, M. Schimerlik, D. Capon, and J Ramachandran
An M2 muscarinic receptor subtype coupled to both adenylyl cyclase and phosphoinositide turnover
Science, October 30, 1987; 238(4827): 672 - 675.
[Abstract] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1985 by the American Society for Pharmacology and Experimental Therapeutics