Abstract
AS THE culmination of a search for endogenous ligands of the opiate receptor1–4, the structures of two closely related pentapeptides, isolated from porcine (brain, with morphine-like properties in pharmacological tests, have been reported by Hughes et al.5 The amino acid sequences of the pentapeptides, termed methionine enkephalin and leucine enkephalin, are Tyr-Gly-Gly-Phe-Met (Met5-enkephalin) and Tyr-Gly-Gly-Phe-Leu (Leu5-enkephalin), respectively. They behave as highly potent opiates in the mouse vas deferens and guinea pig ileum assays5. In addition, animals tolerant to morphine are also tolerant to enkephalin6. The action of the pentapeptides in the guinea pig ileum5 and when injected intracerebrally or intracerebroventricularly7–9 is very short lived, perhaps because of proteolytic degradation. A related peptide, with longer chain length has been shown to have a long duration of action10. Morphine and other narcotics have been shown to bind to the opiate receptor11–13 and inhibit adenylate cyclase activity in homogenates of neuroblastoma × glioma hybrid cells14,15, to inhibit cyclic AMP accumulation in intact hybrid cells15,16 and in rat brain homogenates17. We have tested the effects of Met5- and Leu5-enkephalin on NG108-15 adenylate cyclase activity, and show here that endogenous opiate peptides are potent, receptor-mediated, inhibitors of adenylate cyclase of neuroblastoma × glioma hybrid cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hughes, J., Brain Res., 88, 295–308 (1975).
Terenius, L., and Wahlstrom, A., Acta physiol. scand., 94, 74–81 (1975).
Pasternak, G. W., Goodman, R., and Snyder, S. H., Life Sci., 16, 1765–1769 (1975).
Teschemacher, H., Opheim, K. E., Cox, B. M., and Goldstein, A., Life Sci., 16, 1771–1776 (1975).
Hughes, J. et al., Nature, 258, 577–579 (1975).
Waterfield, A. A., Hughes, J., and Kosterlitz, H. W., Nature, 260, 624–625 (1976).
Belluzzi, J. D., et al., Nature, 260, 625–626 (1976).
Pert, A., Simantov, R., and Snyder, S. H., Proc. natn. Acad, Sci. U.S.A. (in the press).
Chang, J. K., Fong, B., Pert, A., and Pert, C. B., Life Sci. (in the press).
Feldberg, W. S., and Smyth, D. G., J. Physiol. Lond., (in the press).
Pert, C. B., and Snyder, S. H., Science, 179, 1011–1014 (1973).
Terenius, L., Acta Pharmac. Tox., 32, 317–320 (1973).
Simon, E. J., Miller, J. M., and Edelman, I., Proc. natn. Acad. Sci. U.S.A., 70, 1947–1949 (1973).
Klee, W. A., and Nirenberg, M., Proc. natn. Acad. Sci. U.S.A., 71, 3474–3477 (1974).
Sharma, S. K., Nirenberg, M., and Klee, W. A., Proc. natn. Acad. Sci. U.S.A., 72, 590–594 (1975).
Traber, J., Fischer, K., Larzin, S., and Hamprecht, B., Nature, 253, 120–122 (1975).
Collier, H. O. J., and Roy, A. C., Nature, 248, 24–27 (1974); Prostaglandins, 7, 361–376 (1974).
Minna, J., Glazer, D., and Nirenberg, M., Nature new Biol., 235, 225–231 (1972).
Amano, T., Hamprecht, B., and Kemper, W., Expl Cell Res., 85, 399–408 (1974).
Nelson, P., Christian, C., and Nirenberg, M., Proc. natn. Acad. Sci. U.S.A., 73, 123–127 (1976).
Corley, L., Sachs, D. H., and Anfinsen, C. B., Biochem. biophys. Res. Commun., 47, 1353–1359 (1972).
Kosterlitz, H. W., and Watt, A. J., Br. J. Pharmac., 33, 266–276 (1968).
Salomon, Y., Londos, C., and Rodbell, M., Analyt. Biochem., 58, 541–548 (1974).
Cox, B. M., Opheim, K. E., Teschemacher, H., and Goldstein, A., Life Sci., 16, 1777–1782 (1975).
Sharma, S. K., Klee, W. A., and Nirenberg, M., Proc. natn. Acad. Sci. U.S.A., 72, 3092–3096 (1975).
Traber, J., Gullis, R., and Hamprecht, B., Life Sci., 16, 1863–1868 (1975).
Collier, H. O. J., Francis, D. L., McDonald-Gibson, W. J., Roy, A. C., and Saeed, S. A., Life Sci., 17, 85–90 (1975).
Guillemin, R., Ling, N., Burgus, R., C. r. hebd. Séanc. Acad. Sci., Series D., 282, 783–785 (1976).
Li, C. H., and Chung, D., Proc. natn. Acad. Sci. U.S.A., 73, 1145–1148 (1976).
Bradbury, A. F., Smyth, D. G., and Snell, C. R., Nature, 260, 793–795 (1976).
Bradbury, A. F., Smyth, D. G., and Snell, C. R., in Peptides: Chemistry, Structure and Biology (edit. by Walter, R., and Meienhofer, J.), 609–615 (Ann Arbor Science, Inc., 1975).
Li, C. H., Nature, 201, 924 (1964).
Braun, T., Hechter, O., and Li, C. H., The Endocrine Society, Fifty Second Meeting, 48 (1970).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
KLEE, W., NIRENBERG, M. Mode of action of endogenous opiate peptides. Nature 263, 609–612 (1976). https://doi.org/10.1038/263609a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/263609a0
This article is cited by
-
Effects of N-LAAM on [3H]etorphine binding in neuronal-enriched cell cultures
Neurochemical Research (1983)
-
Opioid peptides induce reduction of enkephalin receptors in cultured neuroblastoma cells
Nature (1982)
-
Role of cyclic nucleotides in the mechanism of action of enkephalins
Bulletin of Experimental Biology and Medicine (1982)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.