Desensitization of beta receptor mediated cyclic AMP response of cultured fibroblasts by partial agonists.
Two novel beta-adrenergic myocardial stimulants of general structure: Formula: (see text), where R is a phenyl or benzyl group were investigated for their ability to stimulate and desensitize the cyclic AMP response of C6 glioma cells. Compound ICI 89, 963 (R:phenyl) which elicited less than 1% of the maximum increase in cAMP produced by isoproterenol, was strikingly effective as a desensitizer of the isoproterenol response. This desensitization was markedly reduced by propranolol. Compound ICI 119,033 (R: benzyl) which was a more effective stimulant of cAMP synthesis than ICI 89,963, was also 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 to 3 hours. The data indicate that beta-adrenergic agonists are more potent as desensitizers of the cyclic AMP response than as stimulants of that response.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D005347:Fibroblasts; D005910:Glioma; D006801:Humans; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D007700:Kinetics; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D010726:Phosphodiesterase Inhibitors; D011412:Propanolamines; D011743:Pyrimidines; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D014230:Triazoles; C019227:ICI 89963; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol