title: Alarin 6-25Cys antagonizes alarin-specific effects on food intake and luteinizing hormone secretion.
abstract: Previous data from our labs and from others have demonstrated that intracerebroventricular (ICV) injection of alarin has orexigenic activity and significantly increases plasma luteinizing hormone (LH) secretion in a gonadotropin-releasing hormone (GnRH) dependent manner. The purpose of the current experiments was to determine if the amino acids at the amino-terminal end of the alarin peptide are critical for alarin's effects on reproductive and feeding systems. First, we injected male mice ICV with full-length alarin (Ala1-25) or peptide fragments missing residues at the amino-terminal end (Ala3-25 or Ala6-25 Cys). Neither peptide fragment alone, significantly increased food intake in male mice compared to controls. Second, ICV injection of Ala1-25, but not Ala3-25, significantly (p < 0.01) increased GnRH-mediated LH secretion. Surprisingly, Ala6-25 Cys significantly (p < 0.05) inhibited plasma LH secretion and inhibited Ala1-25 actions. In conclusion, elimination of the first five amino acids of alarin not only abolishes the biological activity of alarin, but becomes an antagonist to alarin-specific effects. Furthermore, Ala6-25 Cys seems to act as a specific antagonist to putative alarin receptors and therefore may be an important tool in identifying alarin-specific receptors.
authors.affiliation: Department of Biology & Neuroscience Program, Hope College, Holland, MI 49423, USA. fraley@hope.edu
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Fraley
authors.forename: Emily
authors.initials: E
authors.lastname: Leathley
authors.forename: Alexis
authors.initials: A
authors.lastname: Nickols
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gerometta
authors.forename: Erika
authors.initials: E
authors.lastname: Coombs
authors.forename: Sarah
authors.initials: S
authors.lastname: Colton
authors.forename: Sara
authors.initials: S
authors.lastname: Gallemore
authors.forename: Abigail
authors.initials: A
authors.lastname: Lindberg
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D044089:Galanin-Like Peptide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology; D007276:Injections, Intraventricular; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology*; D013686:Telemetry
chemical_list: D044089:Galanin-Like Peptide; D010446:Peptide Fragments; C581934:alarin; C582213:alarin 6-25Cys; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone