Agonist-induced desensitization of β-adrenoceptor function in humans: Subtype-selective reduction in β1- or β2-adrenoceptor-mediated physiological effects by xamoterol or procaterol

Abstract

We investigated the effects of β2- (procaterol 2x50 μg/day for 9 days) and β1- (xamoterol 2x200 mg/day for 14 days) adrenoceptor agonists on lymphocyte β2-adrenoceptor density and β1- and β2-adrenoceptor in vivo function (assessed as isoprenaline-infusion-evoked hemodynamic effects and exercise-induced tachycardia) in healthy volunteers. Procaterol decreased lymphocyte β2-adrenoceptor density and all β2-adrenoceptor-mediated in vivo effects but did not affect β1-adrenoceptor-mediated in vivo effects. In contrast, xamoterol neither affected lymphocyte β2-adrenoceptors nor β2-adrenoceptor-mediated in vivo effects but decreased β1-adrenoceptor-mediated in vivo effects. It is concluded that in humans, generally long-term application of β1- or β2-adrenoceptor agonists causes desensitization of β-adrenoceptor function but in a β-adrenoceptor subtype-selective fashion.