Reversal of human lymphocyte β-adrenoceptor desensitization by glucocorticoids

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Abstract
The effect of glucocorticoids on .beta.-agonist-induced desensitization was investigated by studying the effect of a single i.v. dose of methylprednisolone (2 mg/kg) on .beta.-receptor density and affinity in lymphocytes from 4 normal and 4 mildly asthmatic subjects at the end of 3-5 wk of terbutaline therapy and from 4 normal subjects taking no other drug. Terbutaline decreased (-)-[3H]-dihydroalprenolol binding sites by 53% in normal and by 42% in asthmatic subjects. Methylprednisolone restored the number of binding sites to levels statistically indistinguishable from the preterbutaline values in both groups of subjects. In subjects not exposed to terbutaline beforehand, there was no significant alteration in receptor density after methylprednisolone, or in normal lymphocytes incubated in vitro for 90 min with hydrocortisone (10-5 M). No significant change in the Kd was observed in any situation. A single i.v. dose of methylprednisolone reverses terbutaline-induced down-regulation of .beta.-adrenoceptors. This may provide a mechanism for the beneficial effect of steroids in restoring catecholamine responsiveness in asthmatic subjects.