Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Dec 1;90(23):11287–11291. doi: 10.1073/pnas.90.23.11287

Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes.

T Bartfai 1, U Langel 1, K Bedecs 1, S Andell 1, T Land 1, S Gregersen 1, B Ahrén 1, P Girotti 1, S Consolo 1, R Corwin 1, et al.
PMCID: PMC47967  PMID: 7504301

Abstract

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.

Full text

PDF
11287

Images in this article

11289Fig. 2
on p.11289

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amiranoff B., Servin A. L., Rouyer-Fessard C., Couvineau A., Tatemoto K., Laburthe M. Galanin receptors in a hamster pancreatic beta-cell tumor: identification and molecular characterization. Endocrinology. 1987 Jul;121(1):284–289. doi: 10.1210/endo-121-1-284. [DOI] [PubMed] [Google Scholar]
  2. Bartfai T., Bedecs K., Land T., Langel U., Bertorelli R., Girotti P., Consolo S., Xu X. J., Wiesenfeld-Hallin Z., Nilsson S. M-15: high-affinity chimeric peptide that blocks the neuronal actions of galanin in the hippocampus, locus coeruleus, and spinal cord. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10961–10965. doi: 10.1073/pnas.88.23.10961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bartfai T., Fisone G., Langel U. Galanin and galanin antagonists: molecular and biochemical perspectives. Trends Pharmacol Sci. 1992 Aug;13(8):312–317. doi: 10.1016/0165-6147(92)90098-q. [DOI] [PubMed] [Google Scholar]
  4. Bartfai T., Hökfelt T., Langel U. Galanin--a neuroendocrine peptide. Crit Rev Neurobiol. 1993;7(3-4):229–274. [PubMed] [Google Scholar]
  5. Ben-Ari Y. Galanin and Glibenclamide Modulate the Anoxic Release of Glutamate in Rat CA3 Hippocampal Neurons. Eur J Neurosci. 1990 Jan;2(1):62–68. doi: 10.1111/j.1460-9568.1990.tb00381.x. [DOI] [PubMed] [Google Scholar]
  6. Chan-Palay V. Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer's and Parkinson's disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J Comp Neurol. 1988 Jul 22;273(4):543–557. doi: 10.1002/cne.902730409. [DOI] [PubMed] [Google Scholar]
  7. Chen Y., Couvineau A., Laburthe M., Amiranoff B. Solubilization and molecular characterization of active galanin receptors from rat brain. Biochemistry. 1992 Mar 3;31(8):2415–2422. doi: 10.1021/bi00123a029. [DOI] [PubMed] [Google Scholar]
  8. Consolo S., Bertorelli R., Girotti P., La Porta C., Bartfai T., Parenti M., Zambelli M. Pertussis toxin-sensitive G-protein mediates galanin's inhibition of scopolamine-evoked acetylcholine release in vivo and carbachol-stimulated phosphoinositide turnover in rat ventral hippocampus. Neurosci Lett. 1991 May 13;126(1):29–32. doi: 10.1016/0304-3940(91)90363-x. [DOI] [PubMed] [Google Scholar]
  9. Crawley J. N., Austin M. C., Fiske S. M., Martin B., Consolo S., Berthold M., Langel U., Fisone G., Bartfai T. Activity of centrally administered galanin fragments on stimulation of feeding behavior and on galanin receptor binding in the rat hypothalamus. J Neurosci. 1990 Nov;10(11):3695–3700. doi: 10.1523/JNEUROSCI.10-11-03695.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crawley J. N., Robinson J. K., Langel U., Bartfai T. Galanin receptor antagonists M40 and C7 block galanin-induced feeding. Brain Res. 1993 Jan 15;600(2):268–272. doi: 10.1016/0006-8993(93)91382-3. [DOI] [PubMed] [Google Scholar]
  11. Dunning B. E., Taborsky G. J., Jr Galanin--sympathetic neurotransmitter in endocrine pancreas? Diabetes. 1988 Sep;37(9):1157–1162. doi: 10.2337/diab.37.9.1157. [DOI] [PubMed] [Google Scholar]
  12. Dutar P., Lamour Y., Nicoll R. A. Galanin blocks the slow cholinergic EPSP in CA1 pyramidal neurons from ventral hippocampus. Eur J Pharmacol. 1989 May 19;164(2):355–360. doi: 10.1016/0014-2999(89)90477-9. [DOI] [PubMed] [Google Scholar]
  13. Fisone G., Langel U., Carlquist M., Bergman T., Consolo S., Hökfelt T., Undén A., Andell S., Bartfai T. Galanin receptor and its ligands in the rat hippocampus. Eur J Biochem. 1989 Apr 15;181(1):269–276. doi: 10.1111/j.1432-1033.1989.tb14721.x. [DOI] [PubMed] [Google Scholar]
  14. Fisone G., Wu C. F., Consolo S., Nordström O., Brynne N., Bartfai T., Melander T., Hökfelt T. Galanin inhibits acetylcholine release in the ventral hippocampus of the rat: histochemical, autoradiographic, in vivo, and in vitro studies. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7339–7343. doi: 10.1073/pnas.84.20.7339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gregersen S., Lindskog S., Land T., Langel U., Bartfai T., Ahrén B. Blockade of galanin-induced inhibition of insulin secretion from isolated mouse islets by the non-methionine containing antagonist M35. Eur J Pharmacol. 1993 Feb 23;232(1):35–39. doi: 10.1016/0014-2999(93)90725-w. [DOI] [PubMed] [Google Scholar]
  16. Hedlund P. B., Yanaihara N., Fuxe K. Evidence for specific N-terminal galanin fragment binding sites in the rat brain. Eur J Pharmacol. 1992 Dec 2;224(2-3):203–205. doi: 10.1016/0014-2999(92)90806-f. [DOI] [PubMed] [Google Scholar]
  17. Hökfelt T., Millhorn D., Seroogy K., Tsuruo Y., Ceccatelli S., Lindh B., Meister B., Melander T., Schalling M., Bartfai T. Coexistence of peptides with classical neurotransmitters. Experientia. 1987 Jul 15;43(7):768–780. doi: 10.1007/BF01945354. [DOI] [PubMed] [Google Scholar]
  18. Kyrkouli S. E., Stanley B. G., Leibowitz S. F. Galanin: stimulation of feeding induced by medial hypothalamic injection of this novel peptide. Eur J Pharmacol. 1986 Mar 11;122(1):159–160. doi: 10.1016/0014-2999(86)90175-5. [DOI] [PubMed] [Google Scholar]
  19. Langel U., Land T., Bartfai T. Design of chimeric peptide ligands to galanin receptors and substance P receptors. Int J Pept Protein Res. 1992 Jun;39(6):516–522. doi: 10.1111/j.1399-3011.1992.tb00282.x. [DOI] [PubMed] [Google Scholar]
  20. Lindskog S., Ahrén B., Land T., Langel U., Bartfai T. The novel high-affinity antagonist, galantide, blocks the galanin-mediated inhibition of glucose-induced insulin secretion. Eur J Pharmacol. 1992 Jan 14;210(2):183–188. doi: 10.1016/0014-2999(92)90669-u. [DOI] [PubMed] [Google Scholar]
  21. Melander T., Köhler C., Nilsson S., Hökfelt T., Brodin E., Theodorsson E., Bartfai T. Autoradiographic quantitation and anatomical mapping of 125I-galanin binding sites in the rat central nervous system. J Chem Neuroanat. 1988 Jul-Aug;1(4):213–233. [PubMed] [Google Scholar]
  22. Ottlecz A., Samson W. K., McCann S. M. Galanin: evidence for a hypothalamic site of action to release growth hormone. Peptides. 1986 Jan-Feb;7(1):51–53. doi: 10.1016/0196-9781(86)90060-4. [DOI] [PubMed] [Google Scholar]
  23. Palazzi E., Felinska S., Zambelli M., Fisone G., Bartfai T., Consolo S. Galanin reduces carbachol stimulation of phosphoinositide turnover in rat ventral hippocampus by lowering Ca2+ influx through voltage-sensitive Ca2+ channels. J Neurochem. 1991 Mar;56(3):739–747. doi: 10.1111/j.1471-4159.1991.tb01986.x. [DOI] [PubMed] [Google Scholar]
  24. Rossowski W. J., Rossowski T. M., Zacharia S., Ertan A., Coy D. H. Galanin binding sites in rat gastric and jejunal smooth muscle membrane preparations. Peptides. 1990 Mar-Apr;11(2):333–338. doi: 10.1016/0196-9781(90)90089-n. [DOI] [PubMed] [Google Scholar]
  25. Seutin V., Verbanck P., Massotte L., Dresse A. Galanin decreases the activity of locus coeruleus neurons in vitro. Eur J Pharmacol. 1989 May 19;164(2):373–376. doi: 10.1016/0014-2999(89)90481-0. [DOI] [PubMed] [Google Scholar]
  26. Skofitsch G., Sills M. A., Jacobowitz D. M. Autoradiographic distribution of 125I-galanin binding sites in the rat central nervous system. Peptides. 1986 Nov-Dec;7(6):1029–1042. doi: 10.1016/0196-9781(86)90133-6. [DOI] [PubMed] [Google Scholar]
  27. Strosberg A. D. Structure/function relationship of proteins belonging to the family of receptors coupled to GTP-binding proteins. Eur J Biochem. 1991 Feb 26;196(1):1–10. doi: 10.1111/j.1432-1033.1991.tb15778.x. [DOI] [PubMed] [Google Scholar]
  28. Sundström E., Archer T., Melander T., Hökfelt T. Galanin impairs acquisition but not retrieval of spatial memory in rats studied in the Morris swim maze. Neurosci Lett. 1988 Jun 7;88(3):331–335. doi: 10.1016/0304-3940(88)90233-9. [DOI] [PubMed] [Google Scholar]
  29. Wiesenfeld-Hallin Z., Villar M. J., Hökfelt T. The effects of intrathecal galanin and C-fiber stimulation on the flexor reflex in the rat. Brain Res. 1989 May 8;486(2):205–213. doi: 10.1016/0006-8993(89)90506-4. [DOI] [PubMed] [Google Scholar]
  30. Wiesenfeld-Hallin Z., Xu X. J., Langel U., Bedecs K., Hökfelt T., Bartfai T. Galanin-mediated control of pain: enhanced role after nerve injury. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3334–3337. doi: 10.1073/pnas.89.8.3334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wynick D., Smith D. M., Ghatei M., Akinsanya K., Bhogal R., Purkiss P., Byfield P., Yanaihara N., Bloom S. R. Characterization of a high-affinity galanin receptor in the rat anterior pituitary: absence of biological effect and reduced membrane binding of the antagonist M15 differentiate it from the brain/gut receptor. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4231–4235. doi: 10.1073/pnas.90.9.4231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Young W. S., 3rd, Kuhar M. J. A new method for receptor autoradiography: [3H]opioid receptors in rat brain. Brain Res. 1979 Dec 28;179(2):255–270. doi: 10.1016/0006-8993(79)90442-6. [DOI] [PubMed] [Google Scholar]
  33. Zini S., Roisin M. P., Langel U., Bartfai T., Ben-Ari Y. Galanin reduces release of endogenous excitatory amino acids in the rat hippocampus. Eur J Pharmacol. 1993 Mar 15;245(1):1–7. doi: 10.1016/0922-4106(93)90162-3. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES