The pharmacology of α₁-adrenoceptor subtypes

This review examines the functions of α₁-adrenoceptor subtypes, particularly in terms of contraction of smooth muscle. There are 3 subtypes of α₁-adrenoceptor, α_1A- α_1B- and α_1D-adrenoceptors. Evidence is presented that the postulated α_1L-adrenoceptor is simply the native α_1A-adrenoceptor at which prazosin has low potency. In most isolated tissue studies, smooth muscle contractions to exogenous agonists are mediated particularly by α_1A-, with a lesser role for α_1D-adrenoceptors, but α_1B-adrenoceptors are clearly involved in contractions of some tissues, for example, the spleen. However, nerve-evoked responses are the most crucial physiologically, so that these studies of exogenous agonists may overestimate the importance of α_1A-adrenoceptors. The major α₁-adrenoceptors involved in blood pressure control by sympathetic nerves are the α_1D- and the α_1A-adrenoceptors, mediating peripheral vasoconstrictor actions. As noradrenaline has high potency at α_1D-adrenceptors, these receptors mediate the fastest response and seem to be targets for neurally released noradrenaline especially to low frequency stimulation, with α_1A-adrenoceptors being more important at high frequencies of stimulation. This is true in rodent vas deferens and may be true in vasopressor nerves controlling peripheral resistance and tissue blood flow. The α_lA-adrenoceptor may act mainly through Ca²⁺ entry through L-type channels, whereas the α_1D-adrenoceptor may act mainly through T-type channels and exhaustable Ca²⁺ stores. α₁-Adrenoceptors may also act through non-G-protein linked second messenger systems. In many tissues, multiple subtypes of α-adrenoceptor are present, and this may be regarded as the norm rather than exception, although one receptor subtype is usually predominant.