Skip to main content
NCBI 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
. 1981 Oct;78(10):6543–6547. doi: 10.1073/pnas.78.10.6543

Specific receptor for the opioid peptide dynorphin: structure--activity relationships.

C Chavkin, A Goldstein
PMCID: PMC349077  PMID: 6118865

Abstract

The structural features responsible for the high potency and opiate receptor specificity of the opioid peptide dynorphin in the guinea pig ileum myenteric plexus were examined. Successive removal of COOH-terminal amino acids from dynorphin-(1--13) demonstrated important contributions of lysine-13, lysine-11, and arginine-7 to the potency. Removal of the NH2-terminal tyrosine abolished the biologic activity. Several other structural modifications were shown to affect potency: substitution of D-alanine for glycine-2 reduced the potencies of dynorphin-(1--13) amide, -(1--11), and -(1--10); and methyl esterification of the COOH terminus enhanced the potencies of dynorphin-(1--12), -(1--10), -(1--9), -(1--8), and -(1--7). Within the dynorphin sequence, lysine-11 and arginine-7 were found to be important for selectivity of interaction with the dynorphin receptor, which is distinguishable from the mu receptor in this tissue.

Full text

PDF
6543

Images in this article

6546Image
on p.6546

Selected References

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

  1. Chavkin C., Goldstein A. Demonstration of a specific dynorphin receptor in guinea pig ileum myenteric plexus. Nature. 1981 Jun 18;291(5816):591–593. doi: 10.1038/291591a0. [DOI] [PubMed] [Google Scholar]
  2. Ghazarossian V. E., Chavkin C., Goldstein A. A specific radioimmunoassay for the novel opioid peptide dynorphin. Life Sci. 1980 Jul 7;27(1):75–86. doi: 10.1016/0024-3205(80)90021-1. [DOI] [PubMed] [Google Scholar]
  3. Goldstein A., Goldstein J. S., Cox B. M. A synthetic peptide with morphine-like pharmacologic action. Life Sci. 1975 Dec 1;17(11):1643–1654. doi: 10.1016/0024-3205(75)90109-5. [DOI] [PubMed] [Google Scholar]
  4. Goldstein A., Schulz R. Morphine-tolerant longitudinal muscle strip from guinea-pig ileum. Br J Pharmacol. 1973 Aug;48(4):655–666. doi: 10.1111/j.1476-5381.1973.tb08254.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldstein A., Tachibana S., Lowney L. I., Hunkapiller M., Hood L. Dynorphin-(1-13), an extraordinarily potent opioid peptide. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6666–6670. doi: 10.1073/pnas.76.12.6666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Herman B. H., Leslie F., Goldstein A. Behavioral effects and in vivo degradation of intraventricularly administered dynorphin-(1-13) and D-Ala2-dynorphin-(1-11) in rats. Life Sci. 1980 Sep 8;27(10):883–892. doi: 10.1016/0024-3205(80)90084-3. [DOI] [PubMed] [Google Scholar]
  7. Hughes J., Kosterlitz H. W., Leslie F. M. Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antogonist potencies of narcotic analgesics. Br J Pharmacol. 1975 Mar;53(3):371–381. doi: 10.1111/j.1476-5381.1975.tb07373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kangawa K., Matsuo H. alpha-Neo-endorphin : a "big" Leu-enkephalin with potent opiate activity from porcine hypothalami. Biochem Biophys Res Commun. 1979 Jan 15;86(1):153–160. doi: 10.1016/0006-291x(79)90394-2. [DOI] [PubMed] [Google Scholar]
  9. Krebs E. G., Beavo J. A. Phosphorylation-dephosphorylation of enzymes. Annu Rev Biochem. 1979;48:923–959. doi: 10.1146/annurev.bi.48.070179.004423. [DOI] [PubMed] [Google Scholar]
  10. Ling N., Guillemin R. Morphinomimetic activity of synthetic fragments of beta-lipotropin and analogs. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3308–3310. doi: 10.1073/pnas.73.9.3308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lord J. A., Waterfield A. A., Hughes J., Kosterlitz H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977 Jun 9;267(5611):495–499. doi: 10.1038/267495a0. [DOI] [PubMed] [Google Scholar]
  12. Morgan B. A., Smith C. F., Waterfield A. A., Hughes J., Kosterlitz H. W. Structure-activity relationships of methionine-enkephalin. J Pharm Pharmacol. 1976 Aug;28(8):660–661. doi: 10.1111/j.2042-7158.1976.tb02827.x. [DOI] [PubMed] [Google Scholar]
  13. Morley J. S. Structure-activity relationships of enkephalin-like peptides. Annu Rev Pharmacol Toxicol. 1980;20:81–110. doi: 10.1146/annurev.pa.20.040180.000501. [DOI] [PubMed] [Google Scholar]
  14. Orlowski M., Wilk E., Pearce S., Wilk S. Purification and properties of a prolyl endopeptidase from rabbit brain. J Neurochem. 1979 Aug;33(2):461–469. doi: 10.1111/j.1471-4159.1979.tb05176.x. [DOI] [PubMed] [Google Scholar]
  15. Parsons T. F., Preiss J. Biosynthesis of bacterial glycogen. Isolation and characterization of the pyridoxal-P allosteric activator site and the ADP-glucose-protected pyridoxal-P binding site of Escherichia coli B ADP-glucose synthase. J Biol Chem. 1978 Nov 10;253(21):7638–7645. [PubMed] [Google Scholar]
  16. Pert C. B., Pert A., Chang J. K., Fong B. T. (D-Ala2)-Met-enkephalinamide: a potent, long-lasting synthetic pentapeptide analgesic. Science. 1976 Oct 15;194(4262):330–332. doi: 10.1126/science.968485. [DOI] [PubMed] [Google Scholar]
  17. Schwyzer R. ACTH: a short introductory review. Ann N Y Acad Sci. 1977 Oct 28;297:3–26. doi: 10.1111/j.1749-6632.1977.tb41843.x. [DOI] [PubMed] [Google Scholar]
  18. Steiner D. F., Patzelt C., Chan S. J., Quinn P. S., Tager H. S., Nielsen D., Lernmark A., Noyes B. E., Agarwal K. L., Gabbay K. H. Formation of biologically active peptides. Proc R Soc Lond B Biol Sci. 1980 Oct 29;210(1178):45–59. doi: 10.1098/rspb.1980.0117. [DOI] [PubMed] [Google Scholar]
  19. Wüster M., Schulz R., Herz A. Highly specific opiate receptors for dynorphin-(1-13) in the mouse vas deferens. Eur J Pharmacol. 1980 Mar 21;62(2-3):235–236. doi: 10.1016/0014-2999(80)90283-6. [DOI] [PubMed] [Google Scholar]
  20. Wüster M., Schulz R., Herz A. Opiate activity and receptor selectivity of dynorphin1-13 and related peptides. Neurosci Lett. 1980 Oct 20;20(1):79–83. doi: 10.1016/0304-3940(80)90237-2. [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