MOLECULAR CHARACTERIZATION, PHARMACOLOGICAL PROPERTIES AND CHROMOSOMAL LOCALIZATION OF THE HUMAN GALR2 GALANIN RECEPTOR

The neuropeptide galanin mediates a diverse spectrum of biological act ivities by interacting with specific G protein-coupled receptors. We h ave used homology genomic library screening and polymerase chain react ion (PCR) techniques to isolate both genomic and cDNA clones encoding the human homolog of the recently cloned rat GALR2 galanin receptor. B y fluorescence in situ hybridization, the gene encoding human GALR2 (G ALNR2) has been localized to chromosome 17q25.3. The two coding exons of the human GALNR2 gene, interrupted by an intron positioned at the e nd of transmembrane domain III, encode a 387 amino acid G protein-coup led receptor with 87% overall amino acid identity with rat GALR2. In H EK-293 cells stably expressing human GALR2, binding of [I-125]porcine galanin is saturable and can be displaced by galanin, amino-terminal g alanin fragments and chimeric galanin peptides but not by carboxy-term inal galanin fragments. In HEK-293 cells, human GALR2 couples both to G alpha(q/11) to stimulate phospholipase C and increase intracellular calcium levels and to G alpha(i/o) to inhibit forskolin-stimulated int racellular cAMP accumulation. A wide tissue distribution is observed b y reverse transcriptase (RT)-PCR analysis, with human GALR2 mRNA being detected in many areas of the human central nervous system as well as in peripheral tissues. (C) 1998 Elsevier Science B.V. All rights rese rved.