Effects of prednisolone on beta-adrenergic desensitization of normal peripheral lymphocytes: an in vitro model for steroid-controlled tachyphylaxis.
In vitro culture of human peripheral blood lymphocytes with the beta-adrenergic catecholamine isoproterenol for 24 hours, induced homologous beta-adrenergic desensitization, i.e. a large decrease in the number of beta-adrenergic binding sites and loss of the adenylate cyclase response to isoproterenol, without altering the effectiveness of prostaglandin E1 to stimulate the enzyme. Lymphocyte cultures pulsed for 24 hours with isoproterenol, washed free of the agent and cultured in hormone-free medium for 48 hours still showed marked suppression of the beta-adrenergic adenylate cyclase response and a lack of beta-receptors. When prednisolone was added to the isoproterenol-depleted resuspension medium of desensitized lymphocytes, however, the beta-adrenergic system recovered fully within 48 hours. Treatment of desensitized lymphocytes with prednisolone in the continuous presence of isoproterenol failed to restore beta-adrenergic responsiveness of the cells. The results are discussed with respect to the reconstituting effect of prednisolone on beta-adrenergic responsiveness in bronchial asthma after therapy induced tachyphylaxis.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D011239:Prednisolone / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013618:Tachyphylaxis
D011943:Receptors, Adrenergic, beta; D011239:Prednisolone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol