Subtypes of functional alpha1-adrenoceptor

Abstract

In this review, subtypes of functional alpha1-adrenoceptor are discussed. These are cell membrane receptors, belonging to the seven-transmembrane-spanning G-protein-linked family of receptors, which respond to the physiological agonist noradrenaline. alpha1-Adrenoceptors can be divided into alpha1A-, alpha1B- and alpha1D-adrenoceptors, all of which mediate contractile responses involving Gq/11 and inositol phosphate turnover. A fourth alpha1-adrenoceptor, the alpha1L-, represents a functional phenotype of the alpha1A-adrenoceptor. alpha1-Adrenoceptor subtype knock-out mice have refined our knowledge of the functions of alpha-adrenoceptor subtypes, particuarly as subtype-selective agonists and antagonists are not available for all subtypes. alpha1-Adrenoceptors function as stimulatory receptors involved particularly in smooth muscle contraction, especially contraction of vascular smooth muscle, both in local vasoconstriction and in the control of blood pressure and temperature, and contraction of the prostate and bladder neck. Central actions are now being elucidated.

Fig. 1

The historical development of the subclassification of α1-adrenoceptors. For details, see text

Fig. 2

A simplified diagram illustrating the possible ways in which α1-adrenoceptor activation can result in contraction, by Ca²⁺ mobilisation or Ca²⁺ sensitisation. alpha1 alpha1-adrenoceptor, SR sarcoplasmic reticulum, PLC phospholipase C, IP3 inositol triphosphate, DAG diacylgylcerol, PKC protein kinase C, MLCK myosin light chain kinase, MLCP myosin light chain phosphatase, stim stimulate