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 KANOF, P. D.
Right arrow Articles by GREENGARD, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by KANOF, P. D.
Right arrow Articles by GREENGARD, P.

Molecular Pharmacology, Vol 15, 445-461, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Pharmacological Properties of Histamine-Sensitive Adenylate Cyclase from Guinea Pig Cardiac Ventricular Muscle

PHILIP D. KANOF 1 and PAUL GREENGARD 1

1 Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510

An adenylate cyclase that is stimulated by low concentrations of histamine (ka, 6 µM) has been studied in cell-free preparations of guinea pig cardiac ventricular muscle. The characteristics of activation of this adenylate cyclase by histamine receptor agonists, and of inhibition of this enzyme by H2-receptor antagonists (e.g., metiamide, cimetidine), indicate that this histamine-sensitive adenylate cyclase possesses pharmacological properties similar to those of an H2-receptor as defined by physiological experiments in peripheral tissues. Thus, the activation of this adenylate cyclase by histamine may be an early step in the sequence of biochemical events through which histamine acting at H2-receptors exerts its positive inotropic effects on cardiac ventricular muscle. The stimulation of adenylate cyclase activity by histamine was also competitively inhibited by several H1-receptor antagonists (e.g., mepyramine, diphenhydramine, promethazine) and by several imidazole-N-methyl transferase (INMT) inhibitors (e.g., quinacrine, etoprine). The results indicate that many structurally diverse compounds known to interact with various histamine binding proteins (i.e., the H2-receptor, as well as the H1-receptor and the histamine catabolic enzyme INMT) are capable of interacting with H2-receptors coupled to adenylate cyclase in heart. Furthermore, quantitative differences in the inhibition constants of H2-receptor antagonists, H1-receptor antagonists, and INMT inhibitors for the histamine-sensitive adenylate cyclases from guinea pig heart and brain suggest the existence of tissue heterogeneity in the pharmacological properties of H2-receptors.

Submitted on June 2, 1978
Accepted on October 18, 1978




This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
S. J. Hill, C. R. Ganellin, H. Timmerman, J. C. Schwartz, N. P. Shankley, J. M. Young, W. Schunack, R. Levi, and H. L. Haas
International Union of Pharmacology. XIII. Classification of Histamine Receptors
Pharmacol. Rev., September 1, 1997; 49(3): 253 - 278.
[Abstract] [Full Text] [PDF]


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

Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics