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Peptides with Morphine-like Action in the Brain

Published online by Cambridge University Press:  29 January 2018

Hans W. Kosterlitz  and
John Hughes
Hans W. Kosterlitz
Affiliation:
University of Aberdeen, Unit for Research on Addictive Drugs, Marischal College, Aberdeen AB9 1AS
John Hughes
Affiliation:
University of Aberdeen, Unit for Research on Addictive Drugs, Marischal College, Aberdeen AB9 1AS
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Summary

The reasons which led to the search in the brain for substances with morphine-like actions are discussed. Two pentapeptides, methionine-enkephalin and leucine-enkephalin, were isolated. The amino acid sequence of methionine-enkephalin occurs also in the pituitary prohormone β-lipotropin, of which longer fragments (endorphins) of up to 31 amino acids exhibit strong morphine-like action.

The physiological significance of these short and long opioid peptides is discussed, particularly with regard to their possible roles as neurotransmitter or neuromodulator.

With regard to the mechanisms involved in the development of tolerance to and dependence on opiates, the importance of interaction between the endogenous opioid peptides and the exogenous opiate alkaloids is stressed.

The possible therapeutic implications are discussed briefly.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 130 , Issue 3 , March 1977 , pp. 298 - 304
Copyright
Copyright © Royal College of Psychiatrists, 1977 

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References

Akil, H., Mayer, D.J. & Liebeskind, J. C. (1972) Comparison chez le rat entre l'analgésie induite par stimulation de la substance grise péri-aqueducale et l'analgésie morphinique. C.r. hebd. Séanc. Acad. Sci. Paris, 274, 3603–5.Google Scholar
Belluzzi, J. D., Grant, N., Garsky, V., Sarantakis, D., Wise, C. D. & Stein, L. (1976) Analgesia induced in vivo by central administration of enkephalin in rat. Nature, Lond., 260, 625–6.CrossRefGoogle ScholarPubMed
Bradbury, A. F., Smyth, D. G., Snell, C. R., Birdsall, N. J. M. & Hulme, E. C. (1976) C fragment of lipotropin has a high affinity for brain opiate receptors. Nature, Lond., 260, 793–5.Google Scholar
Bradley, P. B., Briggs, E., Gayton, R. J. & Lambert, L. A. (1976) Effects of microiontophoretically applied methionine-enkephalin on single neurones in rat brainstem. Nature, Lond., 261, 425–6.Google Scholar
Büscher, H. H., Hell, R. C., Römer, D., Cardinaux, F., Closse, A., Hauser, D. & Pless, J. (1976) Evidence for analgesic activity of enkephalin in the mouse. Nature, Lond., 261, 423–5.Google Scholar
Cox, B. M., Goldstein, A. & Li, C. H. (1976) Opioid activity of a peptide, β-lipotropin-(61–91), derived from β-lipotropin. Proc. natn. Acad. Sci. U.S.A., 73, 1821–3.Google Scholar
Davies, J. & Dray, A. (1976) Effects of enkephalin and morphine on Renshaw cells in feline spinal cord. Nature, Lond., 262, 603–4.Google Scholar
Feldberg, W. & Smyth, D. G. (1976) The C-fragment of lipotropin—a potent analgesic. J. Physiol. Lond., 260, 30–31P.Google Scholar
Frederickson, R. C. A., Nickander, R., Smithwick, E. L., Shuman, R. & Norris, F. H. (1976) Pharmacological activity of met-enkephalin and analogues in vitro and in vivo. Depression of single neuronal activity in specified brain regions. In Opiates and Endogenous Opioid Peptides (ed. Kosterlitz, H. W.), pp 239–46. Amsterdam: North Holland Publishing Co.Google Scholar
Gent, J. P. & Wolstencroft, J. H. (1976) Effects of methionine-enkephalin and leucine-enkephalin compared with those of morphine on brainstem neurones in cat. Nature, Lond., 261, 426–7.Google Scholar
Guillemin, R., Ling, N. & Burgus, R. (1976) Endorphines, peptides d'origine hypothalamique et neurohypophysaire à activité morphinomimétique. Isolement et structure moléculaire d'α-endorphine. C.r. hebd. Séanc. Acad. Sci. Paris, Sér. D, 282, 783–5.Google Scholar
Hambrook, J. M., Morgan, B. A., Range, M.J. & Smith, C. F. C. (1976) Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates. Nature, Lond., 262, 782–3.Google Scholar
Hill, R. G., Pepper, C. M. & Mitchell, J. F. (1976) Depression of nociceptive and other neurones in the brain by iontophoretically applied met-enkephalin. Nature, Lond., 262, 604–6.CrossRefGoogle ScholarPubMed
Hughes, J., Kosterlitz, H. W. & Leslie, F. M. (1975) Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antagonist potencies of narcotic analgesics. Brit. J. Pharmac., 53, 371–81.Google Scholar
Hughes, J. Smith, T. W., Kosterlitz, H. W., Fothergill, L. A., Morgan, B. A. & Morris, H. R. (1975) Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature, Lond., 258, 577–9.Google Scholar
Klee, W. A., Lampert, A. & Nirenberg, M. (1976) Dual regulation of adenyl cyclase by endogenous opiate peptides. In Opiates and Endogenous Opioid Peptides (ed. Kosterlitz, H. W.), pp 153–9. Amsterdam: North Holland Publishing Co.Google Scholar
Kosterlitz, H. W. & Hughes, J. (1975) Some thoughts on the significance of enkephalin, the endogenous ligand. Life Sci., 17, 91–6.Google Scholar
Kosterlitz, H. W. & Waterfield, A. A. (1975) In vitro models in the study of structure-activity relationships of narcotic analgesics. A. Rev. Pharmac., 15, 29–47.Google Scholar
Kuhar, M. J., Pert, C. B. & Snyder, S. H. (1973) Regional distribution of opiate receptor binding in monkey and human brain. Nature, Lond., 245, 447–50.Google Scholar
Lazarus, L. H., Ling, N. & Guillemin, R. (1976) β-Lipotropin as a prohormone for the morphinomimetic peptides endorphins and enkephalins. Proc. natn. Acad. Sci. U.S.A., 73, 2156–9.Google Scholar
Li, C. H., Barnafi, L., Chrétien, M. & Chung, D. (1965) Isolation and amino-acid sequence of β-LPH from sheep pituitary glands. Nature, Lond., 208, 1093–4.Google Scholar
Li, C. H. & Chung, D. (1976) Primary structure of human β-lipotropin. Nature, Lond., 260, 622–4.Google Scholar
Loh, H. H., Tseng, L. F., Wei, E. & Li, C. H. (1976) β-Endorphin is a potent analgesic agent. Proc. natn. Acad. Sci. U.S.A., 73, 2895–8.CrossRefGoogle ScholarPubMed
Lord, J. A. H., Waterfield, A. A., Hughes, J. & Kosterlitz, H. W. (1976) Multiple opiate receptors. In Opiates and Endogenous Opioid Peptides (ed. Kosterlitz, H. W.), pp 275–80. Amsterdam: North Holland Publishing Co.Google Scholar
Morgan, B. A., Smith, C. F. C., Waterfield, A. A., Hughes, J. & Kosterlitz, H. W. (1976) Structure-activity relationships of methionine-enkephalin. J. Pharm. Pharmac., 28, 660–1.Google Scholar
Pert, A. (1976) Behavioural pharmacology of D-alanine2-methionine-enkephalin amide and other long-acting opiate peptides. In Opiates and Endogenous Opioid Peptides (ed. Kosterlitz, H. W.), pp 87–94. Amsterdam: North Holland Publishing Co.Google Scholar
Pert, C. B., Aposhian, D. & Snyder, S. H. (1974) Phylogenetic distribution of opiate receptor binding. Brain Res., 75, 356–61.Google Scholar
Pert, C. B., Bowie, D. L., Fong, B. T. W. & Chang, J.-K. (1976) Synthetic analogues of met-enkephalin which resist enzymatic destruction. In Opiates and Endogenous Opioid Peptides (ed. Kosterlitz, H. W.), pp 79–86. Amsterdam: North Holland Publishing Co.Google Scholar
Pert, C. B. & Snyder, S. H. (1973) Opiate receptor: demonstration in nervous tissue. Science, N.Y., 179, 1011–14.Google Scholar
Simantov, R. & Snyder, S. H. (1976) Elevated levels of enkephalin in morphine-dependent rats. Nature, Lond., 262, 505–7.Google Scholar
Simantov, R., Snowman, A. M. & Snyder, S. H. (1976) A morphine-like factor ‘enkephalin’ in rat brain: subcellular location. Brain Res., 107, 650–7.Google Scholar
Simon, E. J., Hiller, J. M. & Edelman, I. (1973) Stereo-specific binding of the potent narcotic analgesic 3H-etorphine to rat brain homogenate. Proc. natn. Acad. Sci. U.S.A., 70, 1947–9.Google Scholar
Smith, T. W., Hughes, J., Kosterlitz, H. W. & Sosa, R. P. (1976) Enkephalins: isolation, distribution and function. In Opiates and Endogenous Opioid Peptides (ed. Kosterlitz, H. W.), pp 57–62. Amsterdam: North Holland Publishing Co.Google Scholar
Terenius, L. (1973) Characteristics of the ‘receptor’ for narcotic analgesics in synaptic plasma membrane fraction from rat brain. Acta pharmac. toxic., 33, 377–84.Google Scholar
Wahlström, A., Johansson, L. & Terenius, L. (1976) Characterization of endorphins (endogenous morphine-like factors) in human CSF and brain extracts. In Opiates and Endogenous Opioid Peptides (ed. Kosterlitz, H. W.), pp 49–56. Amsterdam: North Holland Publishing Co.Google Scholar
Waterfield, A. A., Hughes, J. & Kosterlitz, H. W. (1976) Cross tolerance between morphine and methionine-enkephalin. Nature, Lond., 260, 634–5.Google Scholar
Wei, E. & Loh, H. (1976) Chronic, intracerebral infusion of morphine and peptides with osmotic minipumps, and the development of physical dependence. In Opiates and Endogenous Opioid Peptides (ed. Kosterlitz, H. W.), pp 303–10. Amsterdam: North Holland Publishing Co.Google Scholar
Zieglgänsberger, W., Fry, J. P. & Herz, A. (1976) Actions of enkephalin on cortical and striatal neurones of naive and morphine tolerant/dependent rats. In Opiates and Endogenous Opioid Peptides (ed. Kosterlitz, H. W.), pp 231–8. Amsterdam: North Holland Publishing Co.Google Scholar
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