α1-adrenoceptor subtypes

alpha(1)-Adrenoceptors are one of three subfamilies of receptors (alpha(1), alpha(2), beta) mediating responses to adrenaline and noradrenaline. Three alpha(1)-adrenoceptor subtypes are known (alpha(1A), alpha(1B), alpha(1D)) which are all members of the G protein coupled receptor family, and splice variants have been reported in the C-terminus of the alpha(1A). They are expressed in many tissues, particularly smooth muscle where they mediate contraction. Certain subtype-selective agonists and antagonists are now available, and alpha(1A)-adrenoceptor selective antagonists are used to treat benign prostatic hypertrophy. All subtypes activate phospholipase C through the G(q/11) family of G proteins, release stored Ca2+, and activate protein kinase C, although with significant differences in coupling efficiency (alpha(1A) > alpha(1B) > alpha(1D)). Other second messenger pathways are also activated by these receptors, including Ca2+ influx, arachidonic acid release, and phospholipase D. alpha(1)-Adrenoceptors also activate mitogen-activated protein kinase pathways in many cells, and some of these responses are independent of Ca2+ and protein kinase C but involve small G proteins and tyrosine kinases. Direct interactions of alpha(1)-adrenoceptors with proteins other than G proteins have not yet been reported, however there is a consensus binding motif for the immediate early gene Homer in the C-terminal tail of the alpha(1D) subtype. Current research is focused on discovering new subtype-selective drugs, identifying non-traditional signaling pathways activated by these receptors, clarifying how multiple signals are integrated, and identifying proteins interacting directly with the receptors to influence their functions. (C) 1999 Elsevier Science B.V. All rights reserved.