Heterogeneity of alpha-2 adrenergic receptors

Abstract

Alpha adrenergic receptors are subdivided into alpha-1 and alpha-2 subtypes on the basis of their pharmacologic properties. An evaluation of data from radioligand binding and functional experiments indicates that the receptors classified as alpha-2 are not a homogeneous group. The best example of this heterogeneity is the differences in the pharmacologic properties of alpha-2 receptors in rodent and non-rodent mammalian species. Prazosin generally has a high affinity for rodent alpha-2 receptors, but a low affinity for non-rodent alpha-2 receptors, while oxymetazoline is more potent at non-rodent alpha-2 receptors. A definition of alpha-2 adrenergic receptor subtypes is proposed with prazosin having a lower affinity (200-300 nM) at alpha-2A receptors and a higher affinity (5-10 nM) at alpha-2B receptors. Using this definition, the human platelet appears to have only the alpha-2A subtype, while all the receptors in the neonatal rat lung are of the alpha-2B subtype. The rat brain has roughly equal amounts of alpha-2A and -2B receptors while in the rat submandibular gland, about 85% of the receptors are alpha-2A. The ability to pharmacologically define putative alpha-2 adrenergic receptor subtypes should promote the development of additional subtype selective drugs which will increase our understanding of adrenergic pharmacology and may provide new therapeutic approaches.