Alpha-Adrenoceptors in Vascular Smooth Muscle: All Is Not Well

Studies of binding interactions and contractile responses of vascular muscles at α 1 and α2-adrenoceptors revealed the following. (1) Agonists at α1 and α2-adrenoceptors may achieve selectivity by virtue of different efficacies despite similar affinities at the two receptors as well as by differing affinities. This implies that their potencies in binding studies may not correlate with potencies in response and that an agonist may produce positive or negative interactions by occupying both α1- and α2-receptors. (2) Agonists at α2-adrenoceptors have the ability in some vascular muscles to release internal Ca2+ (implying an inositol triphosphate mechanism) as well as open Ca2+ channels. However, their contractile abilities are not closely related to function of Na+/H+ or Na+/Ca2+ exchange sites. Amiloride derivatives probably inhibit contractile effects of α-agonists and K+ elevation by an action at sites distal to the receptor or Ca channels. (3) The failure of α1-agonists to contract arteries in vitro is not related to the absence of these receptors but most likely to their uncoupling from contractile responses, possibly owing to changes related to the in vitro condition (loss of modulating endogenous substances present in vivo such as angiotensin II or endothelins or to changed physical conditions such as may alter function of stretch-activated channels).

Alpha-Adrenoceptors in Vascular Smooth Muscle: All Is Not Well Journal Articles