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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
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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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