JPET Introducing ALZET?ew Model 2006 Pump

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 Gerstin, E. J.
Right arrow Articles by Ehlert, F. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gerstin, E. J.
Right arrow Articles by Ehlert, F. J.

Heparin, dextran and trypan blue allosterically modulate M2 muscarinic receptor binding properties and interfere with receptor-mediated inhibition of adenylate cyclase

EH Gerstin , T Luong and FJ Ehlert

Department of Pharmacology, College of Medicine, University of California, Irvine.

The influences of heparin, dextran and trypan blue on muscarinic receptor binding properties and inhibition of adenylate cyclase were investigated in homogenates of the rat heart. These compounds caused a concentration-dependent enhancement in the specific binding of the muscarinic antagonist [3H]N-methylscopolamine ([3H]NMS) when measured at a radioligand concentration of approximately 0.5 nM in magnesium- containing, low ionic strength buffer. The maximal enhancements of [3H]NMS binding were 2.89-, 1.68- and 1.43-fold increases for heparin, dextran and trypan blue, respectively; the EC50 values for this effect were 0.12, 0.033 and 4.6 microM, respectively. The effects of heparin, dextran and trypan blue on [3H]NMS binding were attributed mainly to an increase in the overall affinity of muscarinic receptors for [3H]NMS, and were greatly attenuated by 100 mM NaCl. These effects were qualitatively similar to those produced by GTP. Heparin, dextran and trypan blue also affected the binding of the muscarinic agonist oxotremorine-M in a manner similar to that of GTP; that is, in the presence of these compounds, agonist affinity was decreased. Our experiments also showed that heparin and dextran attenuate the inhibition of adenylate cyclase activity caused by oxotremorine-M in myocardial homogenates without influencing basal adenylate cyclase activity. We conclude that heparin and dextran interfere with the muscarinic receptor-G protein coupling in the rat heart.

Volume 263, Issue 3, pp. 910-917, 12/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
E. A. Thomas, M. J. Carson, M. J. Neal, and J. G. Sutcliffe
Unique allosteric regulation of 5-hydroxytryptamine receptor-mediated signal transduction by oleamide
PNAS, December 9, 1997; 94(25): 14115 - 14119.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. Tränkle and K. Mohr
Divergent Modes of Action among Cationic Allosteric Modulators of Muscarinic M2 Receptors
Mol. Pharmacol., April 1, 1997; 51(4): 674 - 682.
[Abstract] [Full Text]


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

Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics.