Molecular Pharmacology, Vol 14, 1063-1072, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Correlation between cAMP Production in Guinea-Pig Left and Right Atria and Their Inotropic and Chronotropic Responses to Orciprenaline at Different Temperatures

¹ Department of Applied Pharmacology, Welsh School of Pharmacy, University of Wales Institute of Science and Technology, King Edward VII Avenue, Cardiff CF1 3NU, Great Britain

The positive inotropic responses to catecholamines are potentiated by cooling, whereas the positive chronotropic responses are inhibited. The possible site of this temperature-dependence was examined by determining the cAMP production in paced left and spontaneous right guinea-pig atria during orciprenaline-induced tension and rate responses. The time course of cAMP production preceded that of the respective responses at both 38 and 25°C. cAMP production in the left and right atria 15 seconds after addition of a concentration of orciprenaline (1.4 x 10^-4 M) above that needed for maximum mechanical responses was determined at different temperatures in the presence of theophylline (10^-3 M). These changes were compared with the effects of temperature upon complete tension and rate responses to a submaximal concentration of orciprenaline (9.5 x 10^-8). The increases in cAMP levels in the left and right atria and their respective mechanical responses were affected in parallel by temperature. The optimum temperatures for left (30°C) and right (38°C) atria were the same for cAMP and mechanical response. This close association is further evidence that cAMP plays an important role in these -adrenoceptor mediated responses. Furthermore, the hypothermia-induced supersensitivity of the positive inotropic responses appears to be related to cAMP production.

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ACKNOWLEDGMENTS We are grateful to Dr. J. D. M. Albano, University of Bristol, for guidance with the cAMP assay and for helpful discussions. We also thank Boehringer Ingelheim for the gift of orciprenaline.