Comparison of the effects of xamoterol and isoprenaline on rat cardiac β-adrenoceptors: studies of function and regulation

Publisher Website
Google Scholar
Abstract
1. The effects of the .beta.1-selective partial agonist xamoterol and the full agonist isoprenaline on rat cardiac .beta.-adrenoceptors were compared in funcitonal studies of heart rae response in vivo and in vitro. In addition, the ability of both agents to cause receptor down-regulation in the rat heart following chronic (6 days) subcutaneous infusions was assessed by radioligand binding with [125I]-pindolol. 2. In the functional studies, xamoterol produced a maximal effect equivalent to approximately 39% in ventricular membranes prepared from animals after 6 days of isoprenaline infusion but was unaffected by xamoterol. The relative proportions of the .beta.-adrenoceptor subtypes were unchanged by either active treatment. 4. Plasma xamoterol level at the end of the infusion period was equivalent to that associated with maximum tachycardia in vivo and to the concentration producing maximal stimulation of the rat isolated atrium in vitro. Thus suggesting 100% .beta.-adrenoceptor occupancy during the period of xamoterol infusion. 5. These results indicate that in this animal model xamoterol does not induce cardiac .beta.-adrenoceptor down-regulation during chronic treatment, with doses that produce a maximal functional response both in vitro and in vivo.