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Pharmacol Res. 2001 Sep;44(3):195-208.

Alpha-adrenoceptor subtypes.

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Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Spain.


Different studies have led to our present knowledge of the membrane receptors responsible for mediating the responses to the endogenous catecholamines. These receptors were initially differentiated into alpha - and beta-adrenoceptors. Alpha-adrenoceptors mediate most excitatory functions, and were in turn differentiated in the 1970s into alpha(1)- and alpha(2)-adrenoceptors. The alpha(1)-adrenoceptor type usually mediates responses in the effector organ. The alpha(2)-adrenoceptor type is located presynaptically and regulates the release of the neurotransmitter but it is also present in postsynaptical locations. Both alpha-adrenoceptors are important for the control of vascular tone, but we now know that neither alpha(1)- nor alpha(2)-adrenoceptors constitute homogeneous groups. Each alpha-adrenoceptor type can be subdivided into different subtypes and in this review we have turned our attention to these. The alpha(1)- and the alpha(2)-adrenoceptor subtypes were previously defined pharmacologically by functional and binding studies, and later they were also isolated and identified using cloning methods. In fact, the study of alpha-adrenoceptors was revolutionized by the techniques of molecular biology which permitted us to establish the present classification. The present classification of alpha(1)-adrenoceptors stands as follows: alpha(1A)-adrenoceptor subtype (cloned alpha(1c) and redesignated alpha(1a/c)), alpha(1B)-adrenoceptor subtype (cloned alpha(1b)) and alpha(1D)-adrenoceptor subtype (cloned alpha(1d) and redesignated alpha(1a/d)). It has not been easy to establish the distribution of these alpha(1)-adrenoceptor subtypes in the various organs and tissues, or to define the functional response mediated by each one in the different species studied. Nevertheless it seems that the alpha(1A)-adrenoceptor subtype is more implicated in the maintenance of vascular basal tone and of arterial blood pressure in conscious animals, and the alpha(1B)-adrenoceptor subtype participates more in responses to exogenous agonists. It has also been observed that the expression of the alpha(1B)-adrenoceptor subtype can be modified in pathological situations and particular attention has been paid to the regulation of expression of this receptor. The present classification of alpha(2)-adrenoceptors stands as follows: alpha(2A/D)-adrenoceptor subtype (today it is accepted that the alpha(2A)-adrenoceptor subtype and the alpha(2D)-adrenoceptor subtype are the same receptor but they were identified in different species: the alpha(2A) in human and the alpha(2D) in rat); alpha(2B)-adrenoceptor subtype (cloned alpha(2b)) and alpha(2C)-adrenoceptor subtype (cloned alpha(2c)). Today we know that the alpha(2A/D)- and alpha(2B)-adrenoceptor subtypes in particular control arterial contraction, and that the alpha(2C)-adrenoceptor subtype is responsible above all for venous vasoconstriction. We also know that the alpha(2 A/D)-adrenoceptor subtype fundamentally mediates the central effects of the alpha(2)-adrenoceptor agonists. Despite the validity of the above-mentioned classification of the alpha(1)- and alpha(2)-adrenoceptors, it seems clear that the contractions of a large number of tissues including smooth muscle are mediated by more than one alpha-adrenoceptor subtype. Moreover, few ligands recognise only one alpha-adrenoceptor subtype and the lack of specifity in the different drugs for each one limits their administration in vivo and their therapeutic use.

[Indexed for MEDLINE]

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