Terbutaline-induced desensitization of human lymphocyte beta 2-adrenoceptors. Accelerated restoration of beta-adrenoceptor responsiveness by prednisone and ketotifen.
Open Access
- 1 September 1985
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 76 (3), 1096-1101
- https://doi.org/10.1172/jci112063
Abstract
We investigated, in 36 healthy volunteers, the effects of prednisone and ketotifen on recovery of lymphocyte beta 2-adrenoceptor density (determined by (-)-125iodocyanopindolol binding) and responsiveness (assessed by lymphocyte cyclic AMP [cAMP] responses to 10 microM (-)-isoprenaline) after desensitization by the beta 2-agonist terbutaline. Terbutaline (3 X 5 mg/d) decreased lymphocyte beta 2-adrenoceptor density by approximately 40-50%; concomitantly, lymphocyte cAMP responses to 10 microM (-)-isoprenaline were significantly reduced. After withdrawal of terbutaline beta 2-adrenoceptor, density and responsiveness gradually increased, reaching predrug levels after 4 d. Prednisone (1 X 100 mg orally) accelerated beta 2-adrenoceptor recovery; only 8-10 h after administration of the steroid beta 2-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached values not significantly different from pretreatment levels. Similar effects were obtained with ketotifen (2 mg; thereafter 2 X 1 mg/d for 4 d): 24 h after application of the drug beta 2-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached pretreatment levels. Furthermore, ketotifen simultaneously applied with terbutaline completely prevented terbutaline-induced decrease in lymphocyte beta 2-adrenoceptor density and responsiveness. Prednisone (1 X 100 mg orally) or ketotifen (2 mg; thereafter 2 X 1 mg/d for 2 d) had no significant influence on lymphocyte beta 2-adrenoceptor density in healthy volunteers not pretreated with terbutaline, but shifted the ratio high-to-low affinity state of the lymphocyte beta 2-adrenoceptor toward high affinity state. We conclude that glucocorticoids as well as ketotifen can accelerate recovery of density and responsiveness of lymphocyte beta 2-adrenoceptors desensitized by long-term treatment with beta 2-agonists. Such an effect may have clinical implications for preventing tachyphylaxis of asthmatic patients against therapy with beta 2-agonists.This publication has 48 references indexed in Scilit:
- Beta-Adrenergic Receptors are Different in Subpopulations of Human Circulating LymphocytesJournal of Receptor Research, 1984
- Differences in β‐adrenergic receptor density and adenylate cyclase activity between normal and leukaemic leukocytesEuropean Journal of Clinical Investigation, 1983
- In Vitro Desensitization of Beta Adrenergic Receptors in Human Neutrophils. ATTENUATION BY CORTICOSTEROIDSJCI Insight, 1983
- Lymphocyte beta-adrenergic refractoriness induced by theophylline or metaproterenol in healthy and asthmatic subjectsLife Sciences, 1982
- Adrenergic Receptors in ManNew England Journal of Medicine, 1982
- Clinical implications of drug-induced desensitization of the beta receptor after continuous oral use of terbutalineJournal of Allergy and Clinical Immunology, 1982
- The β-adrenergic receptor in human lymphocytes: Subclassification by the use of a new radio-ligand, (±)−125iodocyanopindololLife Sciences, 1981
- Decreased Beta-Adrenergic Receptors on Polymorphonuclear Leukocytes after Adrenergic TherapyNew England Journal of Medicine, 1978
- $beta;-ADRENERGIC AGONIST RESISTANCE IN NORMAL HUMAN AIRWAYSThe Lancet, 1977
- Subsensitivity of beta responses during therapy with a long-acting beta-2 preparationJournal of Allergy and Clinical Immunology, 1977