Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes
| Autor: | Xiao-Jun Xu, Silvana Consolo, Katarina Bedecs, Zsuzsanna Wiesenfeld-Hallin, Rebecca L. Corwin, Tiit Land, P. Girotti, Siv Andell, Jacqueline N. Crawley, Tomas Hökfelt, Bo Ahrén, Ülo Langel, Sören Gregersen, Tamas Bartfai |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
Agonist endocrine system medicine.medical_specialty medicine.drug_class Molecular Sequence Data Central nervous system Neuropeptide Galanin Galanin receptor Hippocampal formation Biology Ligands Binding Competitive Receptors Gastrointestinal Hormone Rats Sprague-Dawley Internal medicine Insulin Secretion medicine Animals Insulin Amino Acid Sequence Receptor Multidisciplinary digestive oral and skin physiology Feeding Behavior Peptide Fragments Rats Endocrinology medicine.anatomical_structure nervous system Peptides Secretory Rate Receptors Galanin hormones hormone substitutes and hormone antagonists Acetylcholine Research Article medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 90:11287-11291 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.90.23.11287 |
| Popis: | The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 microM) displaces [mono[125I]iodo-Tyr26]galanin from binding sites in the hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent galanin-receptor antagonist: M40, in doses comparable to that of galanin, antagonizes the stimulatory effects of galanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholine release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucose-induced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F cells; instead M40 is a weak agonist at the galanin receptors in these two systems. M40 acts as a weak antagonist of galanin in the spinal flexor reflex model. These results suggest that at least two subtypes of the galanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galanin-receptor subtype (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak agonist. The galanin receptors in the spinal cord occupy an intermediate position between these two putative subtypes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|