title: The novel high-affinity antagonist, galantide, blocks the galanin-mediated inhibition of glucose-induced insulin secretion.
abstract: This study describes the synthesis and effects of the first antagonist to the widely distributed neuropeptide, galanin, which inhibits the secretion of insulin. The first galanin antagonist is a 20-amino acid-long chimeric peptide of the composition galanin-(1-12)-Pro-substance P-(5-11) amide: Gly-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-Gln-Gln-Phe-Phe-Gly- Leu-Met amide. The peptide dose dependently (IC50 = 1.0 nM) antagonizes the galanin-mediated inhibition of the glucose-induced insulin secretion from mouse pancreatic islets. The antagonist was also found to displace 125I-monoiodo-[Tyr26]galanin from membranes of the insulin producing Rin m 5F cells with an IC50 value of less than 0.1 nM. The antagonist is named galantide.
authors.affiliation: Department of Pharmacology, Lund University, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Lindskog
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
authors.forename: T
authors.initials: T
authors.lastname: Land
authors.forename: U
authors.initials: U
authors.lastname: Langel
authors.forename: T
authors.initials: T
authors.lastname: Bartfai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D019004:Galanin / Q000031:analogs & derivatives; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007457:Iodine Radioisotopes; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology*; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry; D013373:Substance P / Q000031:analogs & derivatives*
chemical_list: D007328:Insulin; D007457:Iodine Radioisotopes; D009479:Neuropeptides; D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; C074975:galantide; D013373:Substance P; D019004:Galanin; D005947:Glucose