Skip to main content
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
. 1985 May;82(10):3178–3181. doi: 10.1073/pnas.82.10.3178

Beta-endorphin-(1-27) is a naturally occurring antagonist to etorphine-induced analgesia.

P Nicolas, C H Li
PMCID: PMC397738  PMID: 2987913

Abstract

The potent opioid peptide beta-endorphin is found in the brain and pituitary with two related fragments, beta-endorphin-(1-27) and beta-endorphin-(1-26). The fragments retain substantial opioid-receptor binding activity but are virtually inactive analgesically. beta-Endorphin-(1-27) inhibits beta-endorphin-induced and etorphine-induced analgesia when coinjected intracerebroventricularly into mice. Antagonism by competition at the same site(s) is suggested from parallel shifts of the dose-response curves of etorphine or beta-endorphin in the presence of beta-endorphin-(1-27). Its potency is 4-5 times greater than that of the opiate antagonist naloxone. beta-Endorphin-(1-26) does not antagonize the antinociceptive action of etorphine or beta-endorphin in doses up to 500 pmol per animal.

Full text

PDF

Selected References

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

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blake J., Tseng L. F., Chang W. C., Li C. H. The synthesis and opiate activity of human beta-endorphin analogs. Substituted at residue positions 27 and 31. Int J Pept Protein Res. 1978 May;11(5):323–328. doi: 10.1111/j.1399-3011.1978.tb02856.x. [DOI] [PubMed] [Google Scholar]
  3. Eipper B. A., Mains R. E. Further analysis of post-translational processing of beta-endorphin in rat intermediate pituitary. J Biol Chem. 1981 Jun 10;256(11):5689–5695. [PubMed] [Google Scholar]
  4. Feldberg W., Smyth D. G. C-fragment of lipotropin--an endogenous potent analgesic peptide. Br J Pharmacol. 1977 Jul;60(3):445–453. doi: 10.1111/j.1476-5381.1977.tb07521.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ferrara P., Houghten R., Li C. H. beta-Endorphin: characteristics of binding sites in the rat brain. Biochem Biophys Res Commun. 1979 Aug 13;89(3):786–792. doi: 10.1016/0006-291x(79)91847-3. [DOI] [PubMed] [Google Scholar]
  6. Geisow M. J., Deakin J. F., Dostrovsky J. O., Smyth D. G. Analgesic activity of lipotropin C fragment depends on carboxyl terminal tetrapeptide. Nature. 1977 Sep 8;269(5624):167–168. doi: 10.1038/269167a0. [DOI] [PubMed] [Google Scholar]
  7. Hammonds R. G., Jr, Nicolas P., Li C. H. beta-Endorphin: analgesic and receptor binding activity of non-mammalian homologs. Int J Pept Protein Res. 1982 May;19(5):556–561. doi: 10.1111/j.1399-3011.1982.tb02642.x. [DOI] [PubMed] [Google Scholar]
  8. Hammonds R. G., Jr, Nicolas P., Li C. H. beta-endorphin-(1-27) is an antagonist of beta-endorphin analgesia. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1389–1390. doi: 10.1073/pnas.81.5.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Houghten R. A., Chang W. C., Li C. H. Human beta-endorphin: synthesis and characterization of analogs iodinated and tritiated at tyrosine residues 1 and 27. Int J Pept Protein Res. 1980 Oct;16(4):311–320. doi: 10.1111/j.1399-3011.1980.tb02592.x. [DOI] [PubMed] [Google Scholar]
  10. Koob G. F., Bloom F. E. Behavioural effects of opioid peptides. Br Med Bull. 1983 Jan;39(1):89–94. doi: 10.1093/oxfordjournals.bmb.a071797. [DOI] [PubMed] [Google Scholar]
  11. Li C. H., Yamashiro D., Nicolas P. Beta-endorphin: replacement of tyrosine in position 27 by tryptophan increases analgesic potency--preparation and properties of the 2-nitrophenylsulfenyl derivative. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1042–1044. doi: 10.1073/pnas.79.4.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Li C. H., Yamashiro D., Tseng L. F., Loh H. H. Synthesis and analgesic activity of human beta-endorphin. J Med Chem. 1977 Mar;20(3):325–328. doi: 10.1021/jm00213a001. [DOI] [PubMed] [Google Scholar]
  13. Loh H. H., Tseng L. F., Wei E., Li C. H. beta-endorphin is a potent analgesic agent. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2895–2898. doi: 10.1073/pnas.73.8.2895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mains R. E., Eipper B. A. Differences in the post-translational processing of beta-endorphin in rat anterior and intermediate pituitary. J Biol Chem. 1981 Jun 10;256(11):5683–5688. [PubMed] [Google Scholar]
  15. Ng T. B., Chung D., Li C. H. Isolation and properties of beta-endorphin-(1-27), N alpha-acetyl-beta-endorphin, corticotropin, gamma-lipotropin and neurophysin from equine pituitary glands. Int J Pept Protein Res. 1981 Nov;18(5):443–450. doi: 10.1111/j.1399-3011.1981.tb03005.x. [DOI] [PubMed] [Google Scholar]
  16. Nicolas P., Hammonds R. G., Jr, Li C. H. Beta-endorphin: opiate receptor binding activities of six naturally occurring beta-endorphin homologs studied by using tritiated human hormone and naloxone as primary ligands--effects of sodium ion. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2191–2193. doi: 10.1073/pnas.79.7.2191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nicolas P., Hammonds R. G., Jr, Li C. H. beta-Endorphin-induced analgesia is inhibited by synthetic analogs of beta-endorphin. Proc Natl Acad Sci U S A. 1984 May;81(10):3074–3077. doi: 10.1073/pnas.81.10.3074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Smyth D. G., Massey D. E., Zakarian S., Finnie M. D. Endorphins are stored in biologically active and inactive forms: isolation of alpha-N-acetyl peptides. Nature. 1979 May 17;279(5710):252–254. doi: 10.1038/279252a0. [DOI] [PubMed] [Google Scholar]
  19. Smyth D. G., Snell C. R., Massey D. E. Isolation of the C-fragment and C'-fragment of lipotropin from pig pituitary and C-fragment from brain. Biochem J. 1978 Oct 1;175(1):261–270. doi: 10.1042/bj1750261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Smyth D. G. beta-Endorphin and related peptides in pituitary, brain, pancreas and antrum. Br Med Bull. 1983 Jan;39(1):25–30. doi: 10.1093/oxfordjournals.bmb.a071786. [DOI] [PubMed] [Google Scholar]
  21. Takemori A. E., Hayashi G., Smits S. E. Studies on the quantitative antagonism of analgesics by naloxone and diprenorphine. Eur J Pharmacol. 1972 Oct;20(1):85–92. doi: 10.1016/0014-2999(72)90219-1. [DOI] [PubMed] [Google Scholar]
  22. Takemori A. E., Kupferberg H. J., Miller J. W. Quantitative studies of the antagonism of morphine by nalorphine and naloxone. J Pharmacol Exp Ther. 1969 Sep;169(1):39–45. [PubMed] [Google Scholar]
  23. Yamashiro D., Ferrara P., Li C. H. beta-endorphin: synthesis of analogs with extension at the carboxyl terminus with high radioreceptor binding activity. Int J Pept Protein Res. 1980 Jul;16(1):70–74. doi: 10.1111/j.1399-3011.1980.tb02937.x. [DOI] [PubMed] [Google Scholar]
  24. Yamashiro D., Nicolas P., Li C. H. Synthesis and properties of dermorphin and an analog of beta-endorphin containing the dermorphin sequence. Int J Pept Protein Res. 1983 Mar;21(3):219–222. doi: 10.1111/j.1399-3011.1983.tb03097.x. [DOI] [PubMed] [Google Scholar]
  25. Yeung H. W., Yamashiro D., Chang W. C., Li C. H. Synthesis and opiate activity of human beta-endorphin analogs with various chain lengths. Int J Pept Protein Res. 1978 Jul;12(1):42–46. doi: 10.1111/j.1399-3011.1978.tb02866.x. [DOI] [PubMed] [Google Scholar]
  26. Zakarian S., Smyth D. Distribution of active and inactive forms of endorphins in rat pituitary and brain. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5972–5976. doi: 10.1073/pnas.76.11.5972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zaoral M., Yamashiro D., Hammonds R. G., Jr, Li C. H. Beta-Endorphin: synthesis and radioreceptor binding activity of Beta h-endorphin-(1-27) and its analogs. Int J Pept Protein Res. 1981 Mar;17(3):292–296. doi: 10.1111/j.1399-3011.1981.tb01995.x. [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