The pharmacology of α1-adrenoceptor subtypes

This review examines the functions of alpha(1)-adrenoceptor subtypes, particularly in terms of contraction of smooth muscle. There are 3 subtypes of alpha(1)-adrenoceptor, alpha(1A)-alpha(1B)-and alpha(1D)-adrenoceptors. Evidence is presented that the postulated alpha(1L)-adrenoceptor is simply the native alpha(1A)-adrenoceptor at which prazosin has low potency. In most isolated tissue studies, smooth muscle contractions to exogenous agonists are mediated particularly by alpha(1A)-, with a lesser role for alpha(1D)-adrenoceptors, but alpha(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 alpha(1A)-adrenoceptors. The major alpha(1)-adrenoceptors involved in blood pressure control by sympathetic nerves are the alpha(1D)-and the alpha(1A)-adrenoceptors, mediating peripheral vasoconstrictor actions. As noradrenaline has high potency at alpha(1D)-adrenceptors, these receptors mediate the fastest response and seem to be targets for neurally released noradrenaline especially to low frequency stimulation, with alpha(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 alpha(1A)-adrenoceptor may act mainly through Ca2+ entry through L-type channels, whereas the alpha(1D)-adrenoceptor may act mainly through T-type channels and exhaustable Ca2+ stores. alpha(1)-Adrenoceptors may also act through non-G-protein linked second messenger systems. In many tissues, multiple subtypes of a-adrenoceptor are present, and this may be regarded as the norm rather than exception, although one receptor subtype is usually predominant.