Modulation of beta-adrenergic receptor by hydrocortisone in human polymorphonuclear leukocytes

We have examined the influence of isoproterenol and hydrocortisone on the cycle AMP content and lysosomal enzyme release from highly purified human polymorphonuclear leukocytes. It was found that isoproterenol, although a potent stimulus for cAMP accumulation in human lymphocytes, had only marginal effects on both cAMP content of PMN and enzyme release. Since corticosteroids have been reported to increase the response to beta-agonists in various tissues, it was considered that some of the anti-inflammatory potential of corticosteroids might be related to enhancing the response of PMN to beta-agonists. The influence of hydrocortisone on the response to isoproterenol was accordingly examined. It was found that hydrocortisone did in fact augment the isoproterenol-induced increase in cAMP content. In contrast to the potentiation of cAMP accumulation caused by hydrocortisone and isoproterenol together, the two agents produced only an additional inhibition of enzyme release. Since the inhibition of lysosomal enzyme release from human PMN did not closely reflect the changes observed in the cAMP content, a possible compartmentalization of intracellular cAMP is suggested.