Subtypes of functional alpha1- and alpha2-adrenoceptors

Abstract

In this review, subtypes of functional alpha1- and alpha2-adrenoceptors are discussed. These are cell membrane receptors, belonging to the seven transmembrane spanning G-protein-linked family of receptors, which respond to the physiological agonists noradrenaline and adrenaline. 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 4th alpha1-adrenoceptor, the alpha1L-, has been postulated to mediate contractions in some tissues, but its relationship to cloned receptors remains to be established. Alpha2-adrenoceptors can be divided into alpha2A-, alpha2B- and alpha2C-adrenoceptors, all of which mediate contractile responses. Prejunctional inhibitory alpha2-adrenoceptors are predominantly of the alpha2A-adrenoceptor subtype (the alpha2D-adrenoceptor is a species orthologue), although alpha2C-adrenoceptors may also occur prejunctionally. Although alpha2-adrenoceptors are linked to inhibition of adenylate cyclase, this may not be the primary signal in causing smooth muscle contraction; likewise, prejunctional inhibitory actions probably involve restriction of Ca2+ entry or opening of K+ channels. Receptor knock-out mice are beginning to refine our knowledge of the functions of alpha-adrenoceptor subtypes.