• The first endogenous opiates to be characterized were the enkephalins, two small peptides isolated from pig brain in 1975 by John Hughes and Hans Kosterlitz in Scotland. These two opioid pentapeptides, Met-enkephalin and Leu-enkephalin are only mildly analgesic. When injected directly into the cerebral ventricles, they produce a brief analgesia of approximately 10 min in rats.

    Since the original observations of Hughes and Kosterlitz, 18distinct peptides with opioid activity have been discovered, all of which contain the sequence Tyr-Gly-Gly-Phe. With recombinant DNA techniques, it has been shown that each of these opioid peptides arises from one of three different polyprotein precursors. Each precursor has a molecular weight of about 28,000 and is the product of one of three disticnt genes. The occurrence of a particular coding sequence in genomic DNA can be detected by probing a genomic library (a set of cloned DNA fragments representing the entire genome) with a radioactivity labeled polynucleotide polymer containing the appropriate base sequence.
    Sequence coding for opioid peptides in the genome were first discovered by using cDNA copied from mRNA isolated from tissues prolific in producing the peptides (for example, from the pituitary and the adrenal medulla).


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