DESENSITIZATION OF BETA-RECEPTOR MEDIATED CYCLIC-AMP RESPONSE OF CULTURED FIBROBLASTS BY PARTIAL AGONISTS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 5  (1) , 19-30
Abstract
Two novel .beta.-adrenergic myocardial stimulants of general structure .**GRAPHIC**. where R is a phenyl or benzyl group were studied for their ability to stimulate and desensitize the cyclic[c]AMP response of C6 rat glioma cells. Compound ICI 89,963 (R: phenyl [1-(1-(phenylcarbimido dimethylamino)-p-hydroxyphenoxy)propanol]) which elicited < 1% of the maximum increase in cAMP produced by isoproterenol was effective as an isoproterenol response desensitizer. This desensitization was markedly reduced by propranolol. Compound ICI 119,033 (R: benzyl [1-(1-(benzylcarbimido dimethylamino)-p-hydroxyphenoxy)propanol]) which was a more effective stimulant of cAMP synthesis than ICI 89,963 was a more effective desensitizer of the isoproterenol response of C6 cells. The kinetics of the desensitization by ICI 89,963 were comparable with those for isoproterenol reaching a maximum in 2-3 h. Apparently beta-adrenergic agonists are more potent as desensitizers of the cAMP response than as stimulants of that response.