Galanin-like peptide (GALP) shares partial sequence identity with
galanin and exhibits agonistic activity at two of the
galanin receptor subtypes (GALR1 and GALR2) in vitro. The goal of these experiments was to determine whether
galanin receptors mediate the effects of central GALP administration on food intake,
body weight, and
luteinizing hormone (LH) secretion in the mouse. We first evaluated the effects of intracerebroventricular
injections of GALP or its vehicle alone in GALR1 knockout mice, GALR2 knockout mice, and their respective wild-type controls. GALP reduced food intake and
body weight after 24 h to a similar degree in wild-type, GALR1 knockout, and GALR2 knockout mice. The wild-type, GALR1 knockout, and GALR2 knockout mice also exhibited significant increases in serum levels of LH following the GALP
injections. To help delineate the biologically active moiety of the GALP molecule, we injected wild-type mice with shorter fragments of the full-length
GALP peptide. Neither GALP((1-21)) (the fragment containing the
galanin-homologous sequence) nor GALP((22-60)) (the C-terminal portion of the GALP molecule lacking sequence identity with
galanin) had any discernable effect on food intake,
body weight or circulating LH. These observations demonstrate that neither GALR1 nor GALR2 are essential for mediating the effects of GALP on feeding,
body weight or LH secretion. Furthermore, the
galanin-homologous region of the GALP molecule is not sufficient to mimic the effects of full-length GALP. Together, these findings argue against the hypothesis that GALP signals solely through
galanin receptors in vivoand suggest the existence of a yet-to-be-identified GALP-specific receptor.