Heterogeneity of alpha-2 adrenergic receptors.
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.
Bylund
D B
DB
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002540:Cerebral Cortex / Q000032:analysis; D003000:Clonidine / Q000378:metabolism; D003342:Corpus Striatum / Q000032:analysis; D004285:Dogs; D006168:Guinea Pigs; D006801:Humans; D010109:Oxymetazoline / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity; D013363:Submandibular Gland / Q000032:analysis; D015016:Yohimbine / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D010109:Oxymetazoline; D003000:Clonidine; D011224:Prazosin