Do low-affinity states of β-adrenoceptors have roles in physiology and medicine?

摘要

The pharmacology once ascribed to the 'β_4-adrenoceptor' is now believed to be that of a low-affinity state of the β_1-adrenoceptor. The β_2-adrenoceptor may also have a low-affinity state or site, while the β_3-adrenoceptor - the original low-affinity β-adrenoceptor - can display more than one pharmacology. In this issue, Mallem et al. show that CGP-12177 relaxes thoracic aorta rings from normal rats by stimulating vascular smooth muscle low-affinity β_1-adrenoceptors, apparently linked in part to Gi protein. By contrast, in rings from hypertensive rats, CGP-12177 acts mainly via endothelial β_3-adrenoceptors. This work raises the possibility that low-affinity states of β-adrenoceptors have physiological roles, and suggests that they might be drug targets.