Abstract
The histamine blocking properties of burimamide and promethazine were determined on heart rate and contractility of the right and left atrium of the guinea-pig.
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(1)
The positive chronotropic effect in spontaneously beating guinea-pig atria was competitively blocked by burimamide, but not by promethazine.
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(2)
On the other hand, promethazine proved to be a potent antagonist against the positive inotropic response elicited by histamine on the electrical stimulated (2 Hz) left guinea-pig atrium, whereas burimamide was ineffective.
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(3)
The positive inotropic response to histamine on the right atrium was affected by both antihistaminic drugs investigated. It should, however, be stressed that the blocking efficacy of both antagonists was less pronounced than that evoked by burimamide on the chronotropic and by promethazine on the inotropic effect on right and left atrium, respectively.
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(4)
These results suggest that on guinea-pig heart the positive chronotropic effect elicited by histamine is mediated by ‘burimamide sensitive’ H2-receptors, whereas the positive inotropic effect evoked by histamine is mediated by ‘promethazine sensitive’ H1-receptors. The observation that the positive inotropic effect of histamine on the spontaneously beating right atrium could be antagonized by both types of antihistamines favours the view that part of the positive inotropic response to histamine on this preparation is due to a positive frequency-force relationship (Bowditch-Treppe).
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References
W.D. Flacke, D. Atanackovic, R.A. Gillis andM.H. Alper,The Action of Histamine on the Mammalian Heart, J. Pharmac. exp. Ther.155, 271–278 (1967).
U. Trendelenburg,The Action of Histamine and 5-Hydroxytryptamine on Isolated Mammalian Heart, J. Pharmac. exp. Ther.130, 450–460 (1960).
A.L. Bartlet,The Action of Histamine on the Isolated Heart, Br. J. Pharmac.21, 450–461 (1963).
P.M. Dean,Investigation into the Mode of Action of Histamine on the Isolated Rabbit Heart, Br. J. Pharmac. Chemother.32, 65–77 (1968).
M.J. Hughes andI.A. Coret,On Specificity of Histamine Receptors in the Heart, Am. J. Physiol.223, 1257–1262 (1972).
J.W. Black, W.A.M. Duncan, C.J. Durant, C.R. Ganellin andE.M. Parsons,Definition and Antagonism of Histamine H 2-Receptors, Nature236, 358–390 (1972).
J.H. Wyllie, T. Hesselbo andJ.W. Black,Effects in Man of Histamine H 2-Receptor Blockade by Burimamide, Lancet II, 1117–1120 (1972).
J.W. Black, W.A.M. Duncan, J.C. Emmett, C.R. Ganellin, T. Hesselbo, M.E. Parsons andJ.H. Wyllie,Metiamide — An Orally Active Histamine H 2-Receptor Antagonist, Agents and Actions3, 133–137 (1973).
A.S.F. Ash andH.O. Schild,Receptors Mediating some Actions of Histamine, Br. J. Pharmac. Chemother.27, 427–439 (1966).
G. Pöch, W.R. Kukovetz andN. Scholz,Specific Inhibition by Burimamide of Histamine Effects on Myocardial Contraction and Cyclic AMP, Naunyn-Schmiedebergs Arch. Pharmak.280, 223–228 (1973).
J.M. McNeill andS.C. Verma,Blockade by Burimamide of the Effects of Histamine and Histamine Analogs on Cardiac Contractility, Phosphorylase Activation and Cyclic Adenosine Monophosphate, J. Pharmac. exp. Ther.188, 180–188 (1974).
J.M. Van Rossum,Cumulative Dose-Response Curves II. Technique for the Making of Dose-Response Curves in Isolated Organs and the Evaluation of Drug Parameters, Arch. int. Pharmacodyn.143, 299–330 (1963).
G. Pöch andW.R. Kukovetz,Drug-Induced Release and Pharmacodynamic Effects of Histamine in the Guinea-Pig Heart, J. Pharmac. exp. Ther.156, 522–527 (1967).
I. Klein andG.S. Levey,Activation of Myocardial Adenyl Cyclase by Histamine in Guinea-Pig, Cat and Human Heart, J. Clin. Invest.50, 1012–1015 (1971).
J.M. Mc Neill andL.D. Muschek,Histamine Effects on Cardiac Contractility, Phosporylase and Adenyl Cyclase, J. molec. cell. Cardiol.4, 611–624 (1972).
W.R. Kukovetz, G. Pöch andA. Wurm,Effects of Catecholamines, Histamine and Oxyfedrine on Isotonic Contraction and Cyclic AMP in the Guinea-Pig Heart, Naunyn-Schmiedebergs Arch. Pharmak.278, 403–424 (1973).
B. Katzung, H. Rosin andF. Schneider,Frequency-Force Relationship in the Rabbit Auricle and its Modification by some Metabolic Inhibitors, J. Pharmac. exp. Ther.120, 324–333 (1957).
M. Reiter,Der Einfluss der Natriumionen auf die Beziehung zwischen Frequenz und Kraft der Kontraktion des isolierten Meerschweinchenmyokards, Naunyn-Schmiedebergs Arch. Pharmak. exp. Path.254, 261–286 (1966).
P. Braveny andJ. Sumbera,Electromechanical Correlations in Mammalian Heart Muscle, Pflügers Arch.319, 36–48 (1970).
N.M. Buckley, Z.J. Penefsky andR.S. Litwak,Comparative Force-Frequency Relationship in Human and other Mammalian Ventricular Myocardium, Pflügers Arch.332, 259–270 (1972).
R. Levi,Effects of Exogenous and Immunologically Released Histamine on the Isolated Heart: A Quantitative Comparison, J. Pharmac. exp. Ther.182, 227–238 (1972).
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This work was supported by the Deutsche Forschungsgemeinschaft.
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Reinhardt, D., Wagner, J. & Schümann, H.J. Differentiation of H10and H2-receptors mediating positive chronoand inotropic responses to histamine on atrial preparations of the guinea-pig. Agents and Actions 4, 217–221 (1974). https://doi.org/10.1007/BF01965222
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DOI: https://doi.org/10.1007/BF01965222