Specific inhibition by burimamide of histamine effects on myocardial contraction and cyclic AMP
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In the isolated perfused guinea-pig heart, the increases in isotonic contraction and in cyclic AMP, produced by 2 μg of histamine were significantly and almost completely inhibited in the presence of 2 mg of burimamide, whereas the adrenergic β-receptor blocking drug Kö 592 (50 μg) was ineffective.
Under the same conditions similar effects of 0.1 μg of isoprenaline, which was equieffective with 2 μg of histamine, were not changed by 2 mg of burimamide, but prevented by 50 μg of Kö 592.
The results support the hypothesis, that histamine exerts its cardiac effects by stimulation of a receptor (H2) that can be clearly distinguished from the adrenergic (β1) receptor. The close parallelism between changes in contractile amplitude and in cyclic AMP produced by histamine in the absence and in the presence of burimamide is in accordance with the concept that cyclic AMP mediates the mechanical response of the heart to histamide.
Key wordsHeart-Contraction Cyclic AMP Histamine Burimamide
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- Ash, A. S. F., Schild, H. O.: Receptors mediating some actions of histamine. Brit. J. Pharmacol. 27, 427–439 (1966)Google Scholar
- Bartlet, A. L.: The action of histamine on the isolated heart. Brit. J. Pharmacol. 21, 450–461 (1963)Google Scholar
- Bieck, P. R., Oates, J. A., Robison, G. A., Adkins, R. B.: Cyclic AMP in the regulation of gastric secretion in dogs and humans. Amer. J. Physiol. 224, 158–164 (1973)Google Scholar
- Black, J. W., Duncan, W. A. M., Durant, C. J., Ganellin, C. R., Parsons, E. M.: Definition and antagonism of histamine H2-receptors. Nature (Lond.) 236, 385–390 (1972)Google Scholar
- Dean, P. M.: Investigation into the mode of action of histamine on the isolated rabbit heart. Brit. J. Pharmacol. 32, 65–77 (1968)Google Scholar
- Gilman, A. G.: A protein binding assay for adenosine 3′,5′-cyclic monophosphate. Proc. nat. Acad. Sci. (Wash.) 67, 305–312 (1970)Google Scholar
- Karppanen, H. O., Neuvonen, P. J., Westermann, E.: Effect of some gastric stimulants on the production of cyclic AMP in minced gastric tissue. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, R 35 (1973)Google Scholar
- Klein, I., Levey, G. S.: Activation of myocardial adenylate cyclase by histamine in guinea-pig, cat, and human heart. J. clin. Invest. 50, 1012–1015 (1971)Google Scholar
- Kukovetz, W. R., Pöch, G.: The positive inotropic effect of cyclic AMP. In: Physiology and pharmacology of cyclic AMP. Advanc. Cyclic Nucleotide Res. 1, 261–290 (1972)Google Scholar
- Kukovetz, W. R., Pöch, G., Wurm, A.: Effects of isoprenaline, histamine and oxyfedrine on the cyclic AMP content of the heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, R 70 (1972)Google Scholar
- Kukovetz, W. R., Pöch, G., Wurm, A.: Effect of catecholamines, histamine and oxyfedrine on isotonic contraction and cyclic AMP in the guinea-pig heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 403–424 (1973)Google Scholar
- Mannaioni, P. F.: Interaction between histamine and dichlorisoproterenol, hexamethonium, pempidine, and diphenhydramine, in normal and reserpine-treated heart preparations. Brit. J. Pharmacol. 15, 500–505 (1960)Google Scholar
- McNeill, J. H., Muschek, L. D.: Histamine effects on cardiac contractility, phosphorylase and adenyl cyclase. J. mol. Cell. Cardiol. 4, 611–624 (1972)Google Scholar
- Pöch, G., Kukovetz, W. R.: Drug-induced release and pharmacodynamic effects of histamine in the guinea-pig heart. J. Pharmacol. exp. Ther. 156, 522–527 (1967)Google Scholar
- Pöch, G., Scholz, N., Kukovetz, W. R.: Inhibition of the cardiac effects of histamine on contraction and cyclic AMP by burimamide. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, R 56 (1973)Google Scholar
- Trendelenburg, U.: The action of histamine and 5-hydroxytryptamine on isolated mammalian atria. J. Pharmacol. exp. Ther. 130, 450–460 (1960)Google Scholar