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Molecular Pharmacology, Vol 17, 301-308, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

3H-Glycogen Hydrolysis Elicited by Histamine in Mouse Brain Slices: Selective Involvement of H1 Receptors

TAM THANH QUACH 1, ANNE-MARIE DUCHEMIN 1, CHRISTIANE ROSE 1, and JEAN-CHARLES SCHWARTZ 1

1 Unité de Neurobiologie, Centre Paul Broca, 2 ter, rue d’Alésia, 75014 Paris, France

3H-Glycogen synthesized in mouse cortical slices from 3H-glucose is hydrolyzed in a concentration-dependent manner by histamine with an EC50 of 3·10-6 M. This effect is selectively mediated by H1 receptors. Thus 10-5 M metiamide, a H2-receptor antagonist, did not affect the histamine-induced glycogenolysis, whereas mepyramine, a H1-receptor antagonist, at increasing concentrations progressively shifted the concentration-response curve to the right. Schild plot analysis gives a straight line with a slope close to unity and a pA2 value of 8.0 for mepyramine. In the same way a variety of H1-receptor antagonists, including (+)-chlorpheniramine but not the (-) isomer, at low concentrations progressively inhibited histamine action. On the other hand, dimaprit, a selective H2-receptor agonist, did not elicit any glycogenolytic response even at 3·10-4 M. Other histamine agonists (2-methylhistamine, 2-thiazolylethylamine, and 4-methylhistamine) produced a glycogenolytic effect with relative potencies consistent with stimulation of H1 receptors. When the effects of histamine on the glycogenolytic response and the inhibition of 3H-mepyramine binding are compared, it appears that histamine is substantially weaker in competing with 3H-mepyramine for binding (Ki, 4.5·10-5 M) than in inducing 3H-glycogen hydrolysis (EC50, 3·10-6 M), suggesting that the maximal response is elicited when H1 receptors are only partially occupied. The glycogenolytic response to histamine was markedly reduced when the extracellular calcium ion concentration was reduced to 0.3· 10-3 M. The possibility is raised that the glycogenolytic response to histamine involves calcium as a second messenger, as other responses mediated by H1 receptors.

Submitted on July 30, 1979
Accepted on November 26, 1979






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