Mechanism of glycogenolytic action of histamine in rat hepatocytes.
The mechanism by which histamine induces glycogenolysis was investigated in rat hepatocytes. Histamine induced stimulation of glucose output in hepatocytes in a dose-dependent manner. The maximal effect of the glycogenolytic action of histamine, which was approximately 60% of the maximal glucagon action, was obtained at 10(-6) M. These effects were inhibited by H1 receptor antagonists triprolidine hydrochloride and tripelennamine but not by a H2 receptor antagonist cimetidine. Histamine also increased the activity of phosphorylase a. When 10(-6) M histamine and 5 x 10(-9) M glucagon were added simultaneously, the actions of these two agents were additive. In contrast, there was no additivity when 10(-6) M histamine and 10(-8) M angiotensin II were added. Histamine did not increase adenosine 3',5'-cyclic monophosphate at any doses tested but induced a rapid increase in the cytoplasmic free calcium concentration ([Ca2+]c). Histamine increased [Ca2+]c even in the presence of 1 microM extracellular calcium, an observation suggesting that histamine caused calcium release from an intracellular calcium pool(s). When [3H]inositol-labeled hepatocytes were incubated with histamine, radioactivity in the D-myo-inositol trisphosphate fraction was rapidly increased. These results indicate that histamine acts on rat hepatocytes mainly via H1 receptors and stimulates glycogenolysis by activating the calcium messenger system.
Mine
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Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Kojima
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I
Ogata
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D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010762:Phosphorylase a / Q000378:metabolism; D051381:Rats
D007295:Inositol Phosphates; D000804:Angiotensin II; D006632:Histamine; D006003:Glycogen; D005934:Glucagon; D000242:Cyclic AMP; D010762:Phosphorylase a; D005947:Glucose; D002118:Calcium