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

The pharmacology once ascribed to the 'beta(4)-adrenoceptor' is now believed to be that of a low-affinity state of the beta(1)-adrenoceptor. The beta(2)-adrenoceptor may also have a low-affinity state or site, while the beta(3)-adrenoceptor - the original low-affinity beta-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 beta(1)-adrenoceptors, apparently linked in part to G(i) protein. By contrast, in rings from hypertensive rats, CGP-12177 acts mainly via endothelial beta(3)-adrenoceptors. This work raises the possibility that low- affinity states of beta-adrenoceptors have physiological roles, and suggests that they might be drug targets.