Analysis of the Contribution of Galanin Receptors 1 and 2 to the Central Actions of Galanin-Like Peptide

Vol. 79, No. 5, 2004

Free Abstract Article (Fulltext) Article (PDF 128 KB)

Regulation of Hypothalamic Neurons by Neuropeptides

Analysis of the Contribution of Galanin Receptors 1 and 2 to the Central Actions of Galanin-Like Peptide
Stephanie M. Krasnow^a, John G. Hohmann^d, Alexander Gragerov^d, Donald K. Clifton^b, Robert A. Steiner^a-c

Departments of
^aPhysiology and Biophysics,
^bObstetrics and Gynecology, and
^cBiology, University of Washington, Seattle, Wash., and
^dNura, Inc., Seattle, Wash., USA

Address of Corresponding Author

Neuroendocrinology 2004;79:268-277 (DOI: 10.1159/000079632)

Key Words

Food intake
Knockout mice
GALP
Gonadotropins

Abstract

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.

Author Contacts

Robert A. Steiner
Department of Physiology and Biophysics, University of Washington
Box 357290
Seattle, WA 98195-7290 (USA)
Tel. +1 206 543 8712, Fax +1 206 685 0619, E-Mail steiner@u.washington.edu

Article Information

Received: December 23, 2003
Accepted after revision: April 19, 2004
Published online: July 8, 2004
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 0, Number of References : 35

Medline Abstract (ID 15249737)

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