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Alarin stimulates food intake and gonadotrophin release in male rats
Author(s) -
Boughton CK,
Patterson M,
Bewick GA,
Tadross JA,
Gardiner JV,
Beale KEL,
Chaudery F,
Hunter G,
Busbridge M,
Leavy EM,
Ghatei MA,
Bloom SR,
Murphy KG
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00893.x
Subject(s) - galanin , medicine , endocrinology , galanin receptor , hypothalamus , receptor , neuropeptide , orexigenic , luteinizing hormone , neuropeptide y receptor , gonadotropin releasing hormone , biology , hormone , receptor antagonist , antagonist , chemistry
BACKGROUND AND PURPOSE Alarin is a recently discovered member of the galanin peptide family encoded by a splice variant of galanin‐like peptide (GALP) mRNA. Galanin and GALP regulate energy homeostasis and reproduction. We therefore investigated the effects of alarin on food intake and gonadotrophin release. EXPERIMENTAL APPROACH Alarin was administered into the third cerebral ventricle (i.c.v.) of rats, and food intake or circulating hormone levels were measured. The effect of alarin on the hypothalamo–pituitary–gonadal axis was investigated in vitro using hypothalamic and anterior pituitary explants, and immortalized cell lines. Receptor binding assays were used to determine whether alarin binds to galanin receptors. KEY RESULTS The i.c.v. administration of alarin (30 nmol) to ad libitum fed male rats significantly increased acute food intake to 500%, and plasma luteinizing hormone (LH) levels to 170% of responses to saline. In vitro , 100 nM alarin stimulated neuropeptide Y (NPY) and gonadotrophin‐releasing hormone (GnRH) release from hypothalamic explants from male rats, and 1000 nM alarin increased GnRH release from GT1‐7 cells. In vivo , pretreatment with the GnRH receptor antagonist cetrorelix prevented the increase in plasma LH levels observed following i.c.v. alarin administration. Receptor binding studies confirmed alarin did not bind to any known galanin receptor, or compete with radiolabelled galanin for hypothalamic binding sites. CONCLUSIONS AND IMPLICATIONS These results suggest alarin is a novel orexigenic peptide, and that it increases circulating LH levels via hypothalamic GnRH. Further work is required to identify the receptor(s) mediating the biological effects of alarin.