MOLECULAR-CLONING OF A FUNCTIONAL HUMAN GALANIN RECEPTOR

The ubiquitous neuropeptide galanin controls numerous functions such a s endocrine secretions, intestinal motility, and behavioral activities . These regulatory effects of galanin are mediated through the interac tion with specific membrane receptors and involve the pertussis toxin- sensitive guanine nucleotide binding proteins G(i)/G(o) as transducing elements. We report here the isolation of a cDNA coding for a human g alanin receptor from a Bowes melanoma cell line cDNA expression librar y, by using a radioligand binding strategy. The nucleotide sequence of the cloned receptor reveals an open reading frame encoding a 349-amin o acid protein with seven putative hydrophobic transmembrane domains a nd significant homology with members of the guanine nucleotide binding protein-coupled neuropeptide receptor family, The cloned receptor exp ressed in COS cells specifically binds human, porcine, and rat galanin with high affinity (K-d in the nanomolar range) and mediates the gala nin inhibition of adenylate cyclase. A 2.8-kb galanin receptor transcr ipt was identified in several human tissues. Cloning of this galanin r eceptor should enhance our knowledge of its distribution, structure, a nd function in human physiology and pathophysiology.