The Discovery of Endorphins1

by
Joycelyn Woods

     

For years it had been suspected that opiates had specific binding sites in the brain. There were several attempts to locate these sites, but the existing technologies were unable to distinguish between the non specific binding to tissue and the specific binding to receptors. It must be mentioned here that the first attempt to actually measure specific opiate binding was in the laboratory of Dr. Vincent Dole (Ingolia & Dole, 1970). Although the technology was not available at that time he laid the foundations for the discovery of opiate receptors.

By the early 1970s scientific technology had evolved to the point where the discovery of opiate binding sites seemed almost inevitable. The first to shake the scientific community was Solomon Snyder and his student, Candice Pert of John Hopkins University (Pert & Snyder, 1973). Using a technique developed by Avram Goldstein of Stanford University, Snyder and Pert located the elusive opiate receptor (Goldstein, Lowney & Pal, 1971). That same year two other groups headed by Eric J. Simon of New York University (1973) and Lars Terenious in Uppsala, Sweden (1973) demonstrated specific opiate binding in nervous tissue. The treasure hunt had begun! "For why," Goldstein asked, "would God have made opiate receptors unless he had also made an endogenous morphine-like substance?"

In the mid-1960s Choh Li of the University of California at Berkeley had isolated a pituitary hormone which he named B-Lipotropin (Li, 1964). He noted that one portion of this hormone had analgesic properties. One year after the discovery of the receptor sites John Hughes at the laboratory of Hans Kosterlitz in Aberdeen, Scotland reported the existence of an endogenous morphine-like substance which they later purified and named Enkephalin for "in the head" (Hughes, 1975a; Hughes, 1975b; Kosterlitz, 1976) The Aberdeen group recognized that the peptide sequence of Enkephalin was contained within Li's B-Lipotropin. Li would later name the other endogenous morphine-like peptides, which also come from his pituitary hormone, Endorphin for "morphine within."

Today the term opioid is used for all endogenous morphine-like substances, including Dynorphin another brain opioid peptide system found by Avram Goldstein (Goldstein, Tachibana, Lowney, Hunkapiller & Hood, 1979). Other psychoactive peptides have been discovered and isolated using the techniques developed in these laboratories. In 1978 Solomon Snyder, John Hughes and Hans Kosterlitz shared the Lasker Award for their discoveries. Paralleling the discovery of Enkephalins, Endorphins and opiate receptors have been advances in the field of neuroscience. These advances have led to many exciting discoveries and generated a new interest in the functioning of the brain. We have entered a new era in our understanding of human behavior.

References

Goldstein, A.; Lowney, L.I. and Pal, B.K. Stereospecific and non stereospecific interactions of the morphine congener levorphanol in sub cellular fractions of mouse brain. Proceedings of the National Academy of Science USA 1971 68: 1742-1747.

Goldstein, A.; Tachibana, S.; Lowney, L.I.; Hunkapiller M. and Hood, L. Dynorphin-(1-13), an extraordinary potent opioid peptide. Proceedings of the National Academy of Science USA 1979 76: 6666-6670.

Hughes, J. Isolation of an endogenous compound from the brain with properties similar to morphine. Brain Research 1975 (a), 88: 295-308.

Hughes, J. Search for the endogenous ligand of the opiate receptors. Neuroscience Research Program Bulletin 1975 (b), 13: 55-58.

Ingolia, N.A. and Dole, V.P. Localization of d and l-methadone after intraventricular injection into rat brains. Journal of Pharmacology and Experimental Therapeutics 1970, 175: 84-87.

Kosterlitz, H.W. The incorporation of H3 -glycine into enkephalins in the brains of morphine treated rats. In: Kosterlitz, H.W. (ed), Opiates and Endogenous Opioid Peptides. Amsterdam: North Holland Biomedical Press, 1976.

Li, C.H. Lipotropin: A new active peptide from pituitary glands [abstract]. Nature 1964 201: 924.

Pert, C.B. and Snyder, S. Opiate receptor: Demonstration in nervous tissue. Science 1973, 179: 1011-1014.

Pert, C.B. and Snyder, S. Identification of opiate receptor binding in intact animals. Life Science 1975, 16: 1623-1634.

Simon, E.J.; Hiller, J.M. and Edelman, I. Stereospecific binding of the potent narcotic analgesic (3H) etorphine to rat brain homogenate. Proceedings National Academy of Science USA 1973, 70: 1947-1949.

Terenius, L. Stereospecific interaction between narcotic analgesics and a synaptic plasma membrane fraction of rat cerebral cortex. ACTA Pharmacological Toxicology 1973, 32: 317-320.




Notes


  1. From Methadone Treatment Works: A Compendium For Methadone Maintenance Treatment. NYS Office of Alcoholism and Substance Abuse Services, December 1994. Chemical Dependency Research Working Group.


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