Subtypes of α 1 ‐ and α 2 ‐adrenergic receptors

The adrenergic receptors are members of the superfamily of G protein‐coupled receptors. There are three major types of adrenergic receptors: α 1 , α 2 , and β. Each of these three major types can be divided into three subtypes. Within the α 1 ‐adrenergic receptors, α 1A and the subtypes have been defined pharmacologically on the basis of reversible antagonists, such as WB4101 and phentolamine, and the irreversible antagonist chloroethylclonidine. In at least some tissues the mechanism of action of the α 1A subtype is related to activation of a calcium channel, whereas the α 1B receptor exerts its effect through the second messenger inositol trisphosphate. Both of these receptor subtypes as well as a third, the α 1C , have been identified by molecular cloning. Three pharmacological subtypes of the α 2 ‐adrenergic receptor have also been identified. Prototypic tissues and cell lines in continuous culture have been developed for each of these subtypes, which facilitated their study. The definition of the α 2 subtypes has been based on radioligand binding data and more limited functional data. All three subtypes have been shown to inhibit the activation of adenylate cyclase and thus reduce the levels of cAMP. Three α 2 ‐adrenergic receptor subtypes have been identified by molecular cloning in both the human and rat species. There is reasonable agreement between the pharmacological identified subtypes and those identified by molecular cloning.—Bylund, D. B. Subtypes of α 1 ‐ and α 2 ‐radrenergic receptors. FASEB J. 6: 832‐839; 1992.