CLONING AND CHARACTERIZATION OF THE RAT GALR1 GALANIN RECEPTOR FROM RIN14B INSULINOMA CELLS

Galanin is a ubiquitous neuropeptide that regulates a wide array of ph ysiological processes via interaction with specific G protein-coupled receptors. A rat galanin receptor cDNA was cloned from the Rin14B insu linoma cell line. The isolated cDNA encodes a 346 amino acid G protein -coupled receptor that is 92% identical to the recently reported human GALR1 galanin receptor. [I-125]Galanin binds with high affinity to tw o receptor states in COS1 cell membranes containing the rat GALR1 rece ptor, consistent with coupling of the receptor to a G protein in these membranes. N-terminal galanin fragments and the putative galanin rece ptor antagonists galantide, C7, M35 and M40 bind with high affinity to the rat GALR1 receptor. In contrast, C-terminal galanin fragments do not bind to this receptor. Galanin inhibits basal and forskolin-stimul ated cAMP formation in CHO cells expressing the rat GALR1 receptor via a pertussis toxin-sensitive G protein. The GALR1 receptor is expresse d in rat spinal cord, small intestine, Rin14B insulinoma cells and sev eral brain regions, particularly ventral hippocampus, amygdala, suprao ptic nucleus, hypothalamus, thalamus, lateral parabrachial nucleus and locus coeruleus. Cloning of the rat GALR1 galanin receptor cDNA will permit many new experimental strategies to be applied to studies of th e structure and function of galanin receptors.