Pharmacological characteristics of α₂-adrenergic receptors: Comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning

On the basis of extensive radioligand data and more limited functional data, three pharmacological subtypes of α₂-adrenergic receptors have been identified. More recently, three human genes or cDNAs for α₂-adrenergic receptors have been identified by molecular cloning. The relationship, however, among the pharmacologically defined subtypes and those identified by molecular cloning has not been clear. In order to resolve this issue, we have compared the pharmacological characteristics of the receptors identified by molecular cloning and expressed in COS-7 cells with the characteristics of the pharmacologically defined receptors in their respective prototypic tissue or cell line. The affinities (K_i values) of 12 subtype-selective α₂-adrenergic antagonists were determined for the α₂ receptor in the six preparations, by radioligand binding. Correlation analyses of the pK_i values indicate that the α_2A subtype, as defined in the HT29 cell line, the α_2B receptor of the neonatal rat lung, and the α_2C subtype, as defined in an opossum kidney cell line, correspond to the cloned human α₂-C10, α₂-C2, and α₂-C4 receptor subtypes, respectively.