EXPANSION OF THE ALPHA-2-ADRENERGIC RECEPTOR FAMILY - CLONING AND CHARACTERIZATION OF A HUMAN ALPHA-2-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.