DESENSITIZATION TO THE INOTROPIC EFFECT OF ISOPROTERENOL IN CULTURED VENTRICULAR CELLS

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 223  (1) , 60-67
Abstract
To determine whether monolayers of cultured chick embryo ventricular cells would show tachyphylaxis to chronotropic and inotropic effects of a .beta.-adrenergic agonist, spontaneously contracting monolayers of primary cell cultures were studied using a phase-contrast microscope-video motion detector system that permitted quantitation of the chronotropic and inotropic state. The monolayers were chronotropically unresponsive to isoproterenol between 10-9-10-6 M and chronotropically unresponsive to a 6-fold increase in perfusate Ca concentration. The cells were very inotropically responsive to Ca and isoproterenol. Expressing the isoproterenol inotropic response as a percentage of response to 3.6 mM Ca, the response to 10-6 M isoproterenol was 79 .+-. 4% of the Ca response and the EC50 [median effective concentration] for isoproterenol was 3 .times. 10-9 M. The monolayers rapidly developed dose-dependent desensitization to the inotropic effect of isoproterenol; after a 30-min exposure to 1 .times. 10-6 M isoproterenol, the inotropic response was 40 .+-. 5% of the initial response; desensitization was long-lasting and could be prevented by propranolol. Response to Ca remained unchanged after exposure to 10-6 M isoproterenol. Thus, the cultured cell preparation shows rapid, sustained, .beta.-receptor-specific desensitization to the inotorpic effects of a catecholamine.

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