Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1984 Sep;83(1):271–279. doi: 10.1111/j.1476-5381.1984.tb10143.x

Selectivities of opioid peptide analogues as agonists and antagonists at the delta-receptor.

A D Corbett, M G Gillan, H W Kosterlitz, A T McKnight, S J Paterson, L E Robson
PMCID: PMC1987170  PMID: 6091824

Abstract

The endogenous opioid ligands interact with more than one of the mu-, delta- and kappa-binding sites. By the use of binding assays and bioassays, enkephalin analogues have been assessed for their selectivity for binding at the delta-binding site and for their agonist and antagonist activities at the delta-receptor. The electrically-induced contractions of myenteric plexus-longitudinal muscle preparations of the guinea-pig ileum were inhibited by mu- and kappa-receptor ligands. Inhibitions were seen with mu-, delta- and kappa-receptor ligands in the mouse vas deferens, mainly with mu-receptor ligands in the rat vas deferens and only with kappa-receptor ligands in the rabbit vas deferens. From observations on a considerable number of [Leu5] enkephalin analogues, it has been concluded that [D-Pen2, D-Pen5] enkephalin and [D-Pen2, L-Pen5] enkephalin are the most selective delta-agonists and that N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH is the most selective antagonist (Aib = alpha-aminoisobutyric acid). The binding of these peptides at the delta-site is 99% of the total binding. As to potency, the agonists are superior to the antagonists.

Full text

PDF
271

Selected References

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

  1. Corbett A. D., Paterson S. J., McKnight A. T., Magnan J., Kosterlitz H. W. Dynorphin and dynorphin are ligands for the kappa-subtype of opiate receptor. Nature. 1982 Sep 2;299(5878):79–81. doi: 10.1038/299079a0. [DOI] [PubMed] [Google Scholar]
  2. Cotton R., Giles M. G., Miller L., Shaw J. S., Timms D. ICI 174864: a highly selective antagonist for the opioid delta-receptor. Eur J Pharmacol. 1984 Jan 27;97(3-4):331–332. doi: 10.1016/0014-2999(84)90470-9. [DOI] [PubMed] [Google Scholar]
  3. David M., Moisand C., Meunier J. C., Morgat J. L., Gacel G., Roques B. P. [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr: a specific probe for the delta-opiate receptor subtype in brain membranes. Eur J Pharmacol. 1982 Mar 12;78(3):385–387. doi: 10.1016/0014-2999(82)90046-2. [DOI] [PubMed] [Google Scholar]
  4. Gacel G., Fournie-Zaluski M. C., Roques B. P. D-Tyr--Ser-Gly--Phe--Leu--Thr, a highly preferential ligand for delta-opiate receptors. FEBS Lett. 1980 Sep 8;118(2):245–247. doi: 10.1016/0014-5793(80)80229-8. [DOI] [PubMed] [Google Scholar]
  5. Gillan M. G., Kosterlitz H. W. Spectrum of the mu, delta- and kappa-binding sites in homogenates of rat brain. Br J Pharmacol. 1982 Nov;77(3):461–469. doi: 10.1111/j.1476-5381.1982.tb09319.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Magnan J., Paterson S. J., Tavani A., Kosterlitz H. W. The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties. Naunyn Schmiedebergs Arch Pharmacol. 1982 Jun;319(3):197–205. doi: 10.1007/BF00495865. [DOI] [PubMed] [Google Scholar]
  9. McKnight A. T., Corbett A. D., Kosterlitz H. W. Increase in potencies of opioid peptides after peptidase inhibition. Eur J Pharmacol. 1983 Jan 21;86(3-4):393–402. doi: 10.1016/0014-2999(83)90189-9. [DOI] [PubMed] [Google Scholar]
  10. Mosberg H. I., Hurst R., Hruby V. J., Gee K., Yamamura H. I., Galligan J. J., Burks T. F. Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5871–5874. doi: 10.1073/pnas.80.19.5871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Oka T., Negishi K., Kajiwara M., Watanabe Y., Ishizuka Y., Matsumiya T. The choice of opiate receptor subtype by neo-endorphins. Eur J Pharmacol. 1982 Apr 23;79(3-4):301–305. doi: 10.1016/0014-2999(82)90636-7. [DOI] [PubMed] [Google Scholar]
  12. Oka T., Negishi K., Suda M., Matsumiya T., Inazu T., Ueki M. Rabbit vas deferens: a specific bioassay for opioid kappa-receptor agonists. Eur J Pharmacol. 1981 Jul 17;73(2-3):235–236. doi: 10.1016/0014-2999(81)90098-4. [DOI] [PubMed] [Google Scholar]
  13. Shaw J. S., Miller L., Turnbull M. J., Gormley J. J., Morley J. S. Selective antagonists at the opiate delta-receptor. Life Sci. 1982 Sep 20;31(12-13):1259–1262. doi: 10.1016/0024-3205(82)90356-3. [DOI] [PubMed] [Google Scholar]
  14. Shimohigashi Y., Costa T., Chen H. C., Rodbard D. Dimeric tetrapeptide enkephalins display extraordinary selectivity for the delta opiate receptor. Nature. 1982 May 27;297(5864):333–335. doi: 10.1038/297333a0. [DOI] [PubMed] [Google Scholar]
  15. Shimohigashi Y., Costa T., Matsuura S., Chen H. C., Rodbard D. Dimeric enkephalins display enhanced affinity and selectivity for the delta opiate receptor. Mol Pharmacol. 1982 May;21(3):558–563. [PubMed] [Google Scholar]
  16. Zajac J. M., Gacel G., Petit F., Dodey P., Rossignol P., Roques B. P. Deltakephalin, Tyr-D-Thr-Gly-Phe-Leu-Thr: a new highly potent and fully specific agonist for opiate delta-receptors. Biochem Biophys Res Commun. 1983 Mar 16;111(2):390–397. doi: 10.1016/0006-291x(83)90318-2. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES