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Research ArticleArticle

Action of Histamine on Cyclic AMP in Guinea Pig Gastric Cells: Inhibition by H1- and H2-Receptor Antagonists

SHMUEL BATZRI and JERRY D. GARDNER
Molecular Pharmacology September 1979, 16 (2) 406-416;
SHMUEL BATZRI
Section on Gastroenterology, Digestive Diseases Branch, National Institute of Arthritis, Metabolism and Digestive Disease, National Institutes of Health, Bethesda, Md. 20014
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JERRY D. GARDNER
Section on Gastroenterology, Digestive Diseases Branch, National Institute of Arthritis, Metabolism and Digestive Disease, National Institutes of Health, Bethesda, Md. 20014
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Abstract

In dispersed cells from guinea pig fundic mucosa cyclic AMP was increased 6- to 13-fold by histamine as well as each of 3 chemically related analogues. The relative potencies of these agonists were histamine > 4-methylhistamine > 2-methylhistamine > 2-(2-pyridyl)ethylamine and the relative efficacies of these agents were histamine = 4-methylhistamine > 2-methylhistamine > 2-(2-pyridyl)ethylamine. The increase in cellular cyclic AMP caused by maximally effective concentrations of two agonists in combination was equal to the increase caused by the more effective agonist alone. The increase in cyclic AMP caused by each agonist could be inhibited competitively by metiamide or cimetidine as well as by promethazine or diphenhydramine. The inhibitory potencies of metiamide and cimetidine were greater than those of promethazine and diphenhydramine. Sufficiently high concentrations of each antagonist abolished the action of each agonist and sufficiently high concentrations of each agonist could overcome the inhibition caused by each antagonist. For a given antagonist the inhibitory potency calculated from results with histamine was not significantly different from that calculated from results with each of the other agonists. 2-(2-pyridyl)ethylamine was a partial agonist and its potency as an agonist was equal to its potency as an inhibitor of the action of histamine. These results indicate that in dispersed cells from guinea pig fundic mucosa the increase in cyclic AMP caused by histamine or its 3 analogues can be inhibited competitively by metiamide or cimetidine as well as by classical antihistamines.

ACKNOWLEDGMENT We thank Jean Dyer and Trent Adams for their technical assistance and Mary Ernst for preparing the manuscript.

  • Copyright © 1979 by Academic Press, Inc.

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Molecular Pharmacology
Vol. 16, Issue 2
1 Sep 1979
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Research ArticleArticle

Action of Histamine on Cyclic AMP in Guinea Pig Gastric Cells: Inhibition by H1- and H2-Receptor Antagonists

SHMUEL BATZRI and JERRY D. GARDNER
Molecular Pharmacology September 1, 1979, 16 (2) 406-416;

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Research ArticleArticle

Action of Histamine on Cyclic AMP in Guinea Pig Gastric Cells: Inhibition by H1- and H2-Receptor Antagonists

SHMUEL BATZRI and JERRY D. GARDNER
Molecular Pharmacology September 1, 1979, 16 (2) 406-416;
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