The novel high-affinity antagonist, galantide, blocks the galanin-mediated inhibition of glucose-induced insulin secretion.
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.
Lindskog
S
S
Department of Pharmacology, Lund University, Sweden.
Ahrén
B
B
Land
T
T
Langel
U
U
Bartfai
T
T
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*
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