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Reversal of human lymphocyte β‐adrenoceptor desensitization by glucocorticoids
Author(s) -
Hui Ka Kit P,
Conolly Matthew E,
Tashkin Donald P
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.204
Subject(s) - terbutaline , dihydroalprenolol , methylprednisolone , agonist , endocrinology , medicine , desensitization (medicine) , dissociation constant , receptor , lymphocyte , chemistry , pharmacology , aldosterone , asthma , partial agonist
To investigate the effect of glucocorticoids on β‐agonist‐induced desensitization, we studied the effect of a single intravenous dose of methylprednisolone (2 mg/kg) on β‐receptor density and affinity in lymphocytes from four normal and four mildly asthmatic subjects at the end of 3 to 5 wk of terbutaline therapy and from four normal subjects taking no other drug. Terbutaline decreased (‐) [ 3 H]‐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, nor in normal lymphocytes incubated in vitro for 90 min with hydrocortisone (10 −5 M). No significant change in the dissociation constant was observed in any situation. A single intravenous dose of methylprednisolone reverses terbutaline‐induced down‐regulation of β‐adrenoceptors. This may provide a mechanism for the beneficial effect of steroids in restoring catecholamine responsiveness in asthmatic subjects. Clinical Pharmacology and Therapeutics (1982) 32, 566–571; doi: 10.1038/clpt.1982.204