Studies in vivo and in vitro of terbutaline-induced beta-adrenoceptor desensitization in healthy subjects.

Beta-Adrenoceptor function was studied in eight healthy subjects before, during and 24 and 72 h after cessation of 2 weeks continuous oral treatment with the beta 2-adrenoceptor agonist terbutaline (sustained release, 7.5 mg twice daily). In vivo, blood pressure, heart rate, plasma noradrenaline and plasma cyclic AMP responses to isoprenaline (0.01, 0.02 and 0.05 microgram min-1 kg-1 intravenously) were related to the plasma concentrations of isoprenaline. for comparison, beta 2-adrenoceptor function was evaluated in lymphocytes in vitro by studies of isoprenaline-induced accumulation of cyclic AMP and radioligand binding studies using 125I-iodohydroxybenzylpindolol. In vivo, the beta 2-mediated plasma cyclic AMP response to isoprenaline was markedly attenuated during terbutaline treatment and was still reduced by 38% (P less than 0.05) 72 h after discontinuation of treatment. The blood pressure and heart rate responses to isoprenaline were unaffected by treatment. Isoprenaline-induced elevations of plasma noradrenaline concentrations were markedly reduced during terbutaline treatment. This indicates an attenuation of isoprenaline-induced increases in sympathetic nerve function and could explain why no attenuation of the isoprenaline-induced vasodilatation was observed. Thus, plasma cyclic AMP seems to be a better marker than diastolic blood pressure when evaluating beta 2-adrenoceptor responsiveness in vivo in man, since it is not influenced by counter-regulatory increases in sympathetic nerve activity and/or noradrenaline overflow from sympathetic nerves. In lymphocytes, the isoprenaline-stimulated cyclic AMP accumulation was reduced by 75% and the beta-adrenoceptor binding sites were reduced by 40% 12 h after dosing. Also the lymphocyte beta 2-adrenoceptors recovered slowly after withdrawal of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)