Expansion of the α₂-adrenergic receptor family: Cloning and characterization of a human α₂-adrenergic receptor subtype, the gene for which is located on chromosome 2

Pharmacologic, biochemical, and genetic analyses have demonstrated the existence of multiple α₂-adrenergic receptor (α₂AR) subtypes. We have cloned a human α₂AR by using the polymerase chain reaction with oligonucleotide primers homologous to conserved regions of the previously cloned α₂ARs, the genes for which are located on human chromosomes 4 (C4) and 10 (C10). The deduced amino acid sequence encodes a protein of 450 amino acids whose putative topology is similar to that of the family of guanine nucleotide-binding protein-coupled receptors, but whose structure most closely resembles that of the α₂ARs. Competition curve analysis of the binding properties of the receptor expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique α₂AR pharmacology. Hybridization with somatic cell hybrids shows that the gene for this receptor is located on chromosome 2. Northern blot analysis of various rat tissues shows expression in liver and kidney. The unique pharmacology and tissue localization of this receptor suggest that this is an α₂AR subtype not previously identified by classical pharmacological or ligand binding approaches.