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
. 1994 Oct 25;91(22):10295–10299. doi: 10.1073/pnas.91.22.10295

Skin peptide tyrosine-tyrosine, a member of the pancreatic polypeptide family: isolation, structure, synthesis, and endocrine activity.

A Mor 1, N Chartrel 1, H Vaudry 1, P Nicolas 1
PMCID: PMC45006  PMID: 7937944

Abstract

Pancreatic polypeptide, peptide tyrosine-tyrosine (PYY), and neuropeptide tyrosine (NPY), three members of a family of structurally related peptides, are mainly expressed in the endocrine pancreas, in endocrine cells of the gut, and in the brain, respectively. In the present study, we have isolated a peptide of the pancreatic polypeptide family from the skin of the South American arboreal frog Phyllomedusa bicolor. The primary structure of the peptide was established as Tyr-Pro-Pro-Lys-Pro-Glu-Ser-Pro-Gly-Glu10-Asp-Ala-Ser-Pro-Glu-Glu- Met-Asn- Lys-Tyr20-Leu-Thr-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu30-Val-Thr- Arg-Gln-Arg-Tyr-NH2 . This unusual peptide, named skin peptide tyrosine-tyrosine (SPYY), exhibits 94% similarity with PYY from the frog Rana ridibunda. A synthetic replicate of SPYY inhibits melanotropin release from perifused frog neurointermediate lobes in very much the same way as NPY. These results demonstrate the occurrence of a PYY-like peptide in frog skin. Our data also suggest the existence of a pituitary-skin regulatory loop in amphibians.

Full text

PDF
10295

Selected References

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

  1. Anastasi A., Erspamer V., Bucci M. Isolation and structure of bombesin and alytesin, 2 analogous active peptides from the skin of the European amphibians Bombina and Alytes. Experientia. 1971 Feb 15;27(2):166–167. doi: 10.1007/BF02145873. [DOI] [PubMed] [Google Scholar]
  2. Anastasi A., Erspamer V., Endean R. Isolation and amino acid sequence of caerulein, the active decapeptide of the skin of hyla caerulea. Arch Biochem Biophys. 1968 Apr;125(1):57–68. doi: 10.1016/0003-9861(68)90638-3. [DOI] [PubMed] [Google Scholar]
  3. Bevins C. L., Zasloff M. Peptides from frog skin. Annu Rev Biochem. 1990;59:395–414. doi: 10.1146/annurev.bi.59.070190.002143. [DOI] [PubMed] [Google Scholar]
  4. Blomqvist A. G., Söderberg C., Lundell I., Milner R. J., Larhammar D. Strong evolutionary conservation of neuropeptide Y: sequences of chicken, goldfish, and Torpedo marmorata DNA clones. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2350–2354. doi: 10.1073/pnas.89.6.2350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bulant M., Richter K., Kuchler K., Kreil G. A cDNA from brain of Xenopus laevis coding for a new precursor of thyrotropin-releasing hormone. FEBS Lett. 1992 Jan 27;296(3):292–296. doi: 10.1016/0014-5793(92)80307-3. [DOI] [PubMed] [Google Scholar]
  6. Böttcher G., Sjöberg J., Ekman R., Håkanson R., Sundler F. Peptide YY in the mammalian pancreas: immunocytochemical localization and immunochemical characterization. Regul Pept. 1993 Feb 18;43(3):115–130. doi: 10.1016/0167-0115(93)90146-y. [DOI] [PubMed] [Google Scholar]
  7. Chartrel N., Conlon J. M., Danger J. M., Fournier A., Tonon M. C., Vaudry H. Characterization of melanotropin-release-inhibiting factor (melanostatin) from frog brain: homology with human neuropeptide Y. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3862–3866. doi: 10.1073/pnas.88.9.3862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chronwall B. M., DiMaggio D. A., Massari V. J., Pickel V. M., Ruggiero D. A., O'Donohue T. L. The anatomy of neuropeptide-Y-containing neurons in rat brain. Neuroscience. 1985 Aug;15(4):1159–1181. doi: 10.1016/0306-4522(85)90260-x. [DOI] [PubMed] [Google Scholar]
  9. Conlon J. M., Balasubramaniam A., Hazon N. Structural characterization and biological activity of a neuropeptide Y-related peptide from the dogfish, Scyliorhinus canicula. Endocrinology. 1991 May;128(5):2273–2279. doi: 10.1210/endo-128-5-2273. [DOI] [PubMed] [Google Scholar]
  10. Conlon J. M., Bjenning C., Hazon N. Structural characterization of neuropeptide Y from the brain of the dogfish, Scyliorhinus canicula. Peptides. 1992 May-Jun;13(3):493–497. doi: 10.1016/0196-9781(92)90080-m. [DOI] [PubMed] [Google Scholar]
  11. Conlon J. M., Bjenning C., Moon T. W., Youson J. H., Thim L. Neuropeptide Y-related peptides from the pancreas of a teleostean (eel), holostean (bowfin) and elasmobranch (skate) fish. Peptides. 1991 Mar-Apr;12(2):221–226. doi: 10.1016/0196-9781(91)90003-8. [DOI] [PubMed] [Google Scholar]
  12. Conlon J. M., Bjørnholm B., Jørgensen F. S., Youson J. H., Schwartz T. W. Primary structure and conformational analysis of peptide methionine-tyrosine, a peptide related to neuropeptide Y and peptide YY isolated from lamprey intestine. Eur J Biochem. 1991 Jul 15;199(2):293–298. doi: 10.1111/j.1432-1033.1991.tb16123.x. [DOI] [PubMed] [Google Scholar]
  13. Conlon J. M., Chartrel N., Vaudry H. Primary structure of frog PYY: implications for the molecular evolution of the pancreatic polypeptide family. Peptides. 1992 Jan-Feb;13(1):145–149. doi: 10.1016/0196-9781(92)90154-u. [DOI] [PubMed] [Google Scholar]
  14. DE P., CHATTERJEE R. Nucleolar localization of succinic dehydrogenase in human malignant cells with MTT. Experientia. 1962 Dec 15;18:562–562. doi: 10.1007/BF02172179. [DOI] [PubMed] [Google Scholar]
  15. Danger J. M., Leboulenger F., Guy J., Tonon M. C., Benyamina M., Martel J. C., Saint-Pierre S., Pelletier G., Vaudry H. Neuropeptide Y in the intermediate lobe of the frog pituitary acts as an alpha-MSH-release inhibiting factor. Life Sci. 1986 Sep 29;39(13):1183–1192. doi: 10.1016/0024-3205(86)90350-4. [DOI] [PubMed] [Google Scholar]
  16. Erspamer V., Melchiorri P., Falconieri Erspamer G., Montecucchi P. C., de Castiglione R. Phyllomedusa skin: a huge factory and store-house of a variety of active peptides. Peptides. 1985;6 (Suppl 3):7–12. doi: 10.1016/0196-9781(85)90343-2. [DOI] [PubMed] [Google Scholar]
  17. Erspamer V., Melchiorri P., Nakajima T., Yasuhara T., Endean R. Amino acid composition and sequence of crinia-angiotensin, an angiotensin II-like endecapeptide from the skin of the Australian frog Crinia georgiana. Experientia. 1979 Sep 15;35(9):1132–1133. doi: 10.1007/BF01963240. [DOI] [PubMed] [Google Scholar]
  18. Falconieri Erspamer G., Severini C., Erspamer V., Melchiorri P., Delle Fave G., Nakajima T. Parallel bioassay of 27 bombesin-like peptides on 9 smooth muscle preparations. Structure-activity relationships and bombesin receptor subtypes. Regul Pept. 1988 May;21(1-2):1–11. doi: 10.1016/0167-0115(88)90085-7. [DOI] [PubMed] [Google Scholar]
  19. Higgins D. G., Sharp P. M. Fast and sensitive multiple sequence alignments on a microcomputer. Comput Appl Biosci. 1989 Apr;5(2):151–153. doi: 10.1093/bioinformatics/5.2.151. [DOI] [PubMed] [Google Scholar]
  20. Jensen J., Conlon J. M. Characterization of peptides related to neuropeptide tyrosine and peptide tyrosine-tyrosine from the brain and gastrointestinal tract of teleost fish. Eur J Biochem. 1992 Dec 1;210(2):405–410. doi: 10.1111/j.1432-1033.1992.tb17435.x. [DOI] [PubMed] [Google Scholar]
  21. Kimmel J. R., Pollock H. G., Hazelwood R. L. Isolation and characterization of chicken insulin. Endocrinology. 1968 Dec;83(6):1323–1330. doi: 10.1210/endo-83-6-1323. [DOI] [PubMed] [Google Scholar]
  22. Kuchler K., Richter K., Trnovsky J., Egger R., Kreil G. Two precursors of thyrotropin-releasing hormone from skin of Xenopus laevis. Each contains seven copies of the end product. J Biol Chem. 1990 Jul 15;265(20):11731–11733. [PubMed] [Google Scholar]
  23. Larhammar D., Blomqvist A. G., Söderberg C. Evolution of neuropeptide Y and its related peptides. Comp Biochem Physiol C. 1993 Nov;106(3):743–752. doi: 10.1016/0742-8413(93)90236-e. [DOI] [PubMed] [Google Scholar]
  24. Lazarus L. H., Attila M. The toad, ugly and venomous, wears yet a precious jewel in his skin. Prog Neurobiol. 1993 Oct;41(4):473–507. doi: 10.1016/0301-0082(93)90027-p. [DOI] [PubMed] [Google Scholar]
  25. Montecucchi P. C., Anastasi A., de Castiglione R., Erspamer V. Isolation and amino acid composition of sauvagine. An active polypeptide from methanol extracts of the skin of the South American frog Phyllomedusa sauvagei. Int J Pept Protein Res. 1980 Sep;16(3):191–199. [PubMed] [Google Scholar]
  26. Mor A., Amiche M., Nicolas P. Enter a new post-translational modification: D-amino acids in gene-encoded peptides. Trends Biochem Sci. 1992 Dec;17(12):481–485. doi: 10.1016/0968-0004(92)90333-5. [DOI] [PubMed] [Google Scholar]
  27. Mor A., Amiche M., Nicolas P. Structure, synthesis, and activity of dermaseptin b, a novel vertebrate defensive peptide from frog skin: relationship with adenoregulin. Biochemistry. 1994 May 31;33(21):6642–6650. doi: 10.1021/bi00187a034. [DOI] [PubMed] [Google Scholar]
  28. Mor A., Nguyen V. H., Delfour A., Migliore-Samour D., Nicolas P. Isolation, amino acid sequence, and synthesis of dermaseptin, a novel antimicrobial peptide of amphibian skin. Biochemistry. 1991 Sep 10;30(36):8824–8830. doi: 10.1021/bi00100a014. [DOI] [PubMed] [Google Scholar]
  29. Mor A., Nicolas P. Isolation and structure of novel defensive peptides from frog skin. Eur J Biochem. 1994 Jan 15;219(1-2):145–154. doi: 10.1111/j.1432-1033.1994.tb19924.x. [DOI] [PubMed] [Google Scholar]
  30. Nakajima T., Yasuhara T., Erspamer G. F., Visser J. Occurrence of Hyp3-bradykinin in methanol extracts of the skin of the South African leptodactylid frog Heleophryne purcelli. Experientia. 1979 Sep 15;35(9):1133–1133. doi: 10.1007/BF01963241. [DOI] [PubMed] [Google Scholar]
  31. Pieribone V. A., Brodin L., Friberg K., Dahlstrand J., Söderberg C., Larhammar D., Hökfelt T. Differential expression of mRNAs for neuropeptide Y-related peptides in rat nervous tissues: possible evolutionary conservation. J Neurosci. 1992 Sep;12(9):3361–3371. doi: 10.1523/JNEUROSCI.12-09-03361.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pollock H. G., Hamilton J. W., Rouse J. B., Ebner K. E., Rawitch A. B. Isolation of peptide hormones from the pancreas of the bullfrog (Rana catesbeiana). Amino acid sequences of pancreatic polypeptide, oxyntomodulin, and two glucagon-like peptides. J Biol Chem. 1988 Jul 15;263(20):9746–9751. [PubMed] [Google Scholar]
  33. Simmaco M., Mignogna G., Barra D., Bossa F. Novel antimicrobial peptides from skin secretion of the European frog Rana esculenta. FEBS Lett. 1993 Jun 14;324(2):159–161. doi: 10.1016/0014-5793(93)81384-c. [DOI] [PubMed] [Google Scholar]
  34. Söderberg C., Pieribone V. A., Dahlstrand J., Brodin L., Larhammar D. Neuropeptide role of both peptide YY and neuropeptide Y in vertebrates suggested by abundant expression of their mRNAs in a cyclostome brain. J Neurosci Res. 1994 Apr 1;37(5):633–640. doi: 10.1002/jnr.490370510. [DOI] [PubMed] [Google Scholar]
  35. Tatemoto K., Carlquist M., Mutt V. Neuropeptide Y--a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature. 1982 Apr 15;296(5858):659–660. doi: 10.1038/296659a0. [DOI] [PubMed] [Google Scholar]
  36. Tatemoto K. Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2514–2518. doi: 10.1073/pnas.79.8.2514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tonon M. C., Leroux P., Leboulenger F., Delarue C., Jégou S., Vaudry H. Thyrotropin-releasing hormone stimulates the release of melanotropin from frog neurointermediate lobes in vitro. Life Sci. 1980 Mar 17;26(11):869–875. doi: 10.1016/0024-3205(80)90349-5. [DOI] [PubMed] [Google Scholar]
  38. Tonon M. C., Leroux P., Stoeckel M. E., Jegou S., Pelletier G., Vaudry H. Catecholaminergic control of alpha-melanocyte-stimulating hormone (alpha MSH) release by frog neurointermediate lobe in vitro: evidence for direct stimulation of alpha MSH release by thyrotropin-releasing hormone. Endocrinology. 1983 Jan;112(1):133–141. doi: 10.1210/endo-112-1-133. [DOI] [PubMed] [Google Scholar]
  39. Valentijn J. A., Vaudry H., Kloas W., Cazin L. Melanostatin (NPY) inhibited electrical activity in frog melanotrophs through modulation of K+, Na+ and Ca2+ currents. J Physiol. 1994 Mar 1;475(2):185–195. doi: 10.1113/jphysiol.1994.sp020060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Vaudry H., Tonon M. C., Delarue C., Vaillant R., Kraicer J. Biological and radioimmunological evidence for melanocyte stimulating hormones (MSH) of extrapituitary origin in the rat brain. Neuroendocrinology. 1978;27(1-2):9–24. doi: 10.1159/000122796. [DOI] [PubMed] [Google Scholar]
  41. Verburg-van Kemenade B. M., Jenks B. G., Danger J. M., Vaudry H., Pelletier G., Saint-Pierre S. An NPY-like peptide may function as MSH-release inhibiting factor in Xenopus laevis. Peptides. 1987 Jan-Feb;8(1):61–67. doi: 10.1016/0196-9781(87)90166-5. [DOI] [PubMed] [Google Scholar]
  42. Wahlestedt C., Reis D. J. Neuropeptide Y-related peptides and their receptors--are the receptors potential therapeutic drug targets? Annu Rev Pharmacol Toxicol. 1993;33:309–352. doi: 10.1146/annurev.pa.33.040193.001521. [DOI] [PubMed] [Google Scholar]
  43. Wilbur W. J., Lipman D. J. Rapid similarity searches of nucleic acid and protein data banks. Proc Natl Acad Sci U S A. 1983 Feb;80(3):726–730. doi: 10.1073/pnas.80.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Yasuhara T., Nakajima T. Letter: Occurrence of Pyr-His-Pro-NH2 in the frog skin. Chem Pharm Bull (Tokyo) 1975 Dec;23(12):3301–3303. doi: 10.1248/cpb.23.3301. [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