alpha(1)-adrenoceptor subtypes

作者：Zhong HY; Minneman KP^*

来源：European Journal of Pharmacology, 1999, 375(1-3): 261-276.

DOI：10.1016/S0014-2999(99)00222-8

• adrenoceptor
• noradrenaline
• adrenaline
• mitogenic signaling
• Ca2+

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.

• 出版日期1999-6-30