Enkephalins, dynorphins and β-endorphin are endogenous opiate-like substances that are differentially distributed among vertebrate taxa. Enkephalins have the widest distribution, and the proenkephalin gene would appear to represent the ancestral opioid gene. This review will consider the following hypothesis: the evolution of the opioids occurred as a result of two duplications of the proenkephalin gene. In this hypothesis, the first duplication event would have given rise to the proopiomelanocortin gene, the precursor for β-endorphin, and the second duplication event would have given rise to the prodynorphin gene.

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