The ectoenzyme-mediated metabolism of neuropeptides may be an important regulatory site of peptide-mediated activity. These membrane-bound, extracellularly oriented peptidases are not only responsible for inactivating peptide substrates, but also lead to the formation of metabolic fragments. Peptide fragments formed after enzymatic proteolysis have been shown to display novel bioactivity as a consequence of a shift in receptor selectivity. This example of nervous system plasticity through peptide biotransformation can have multiple consequences. Centrally acting drugs have been shown to have profound effects on peptide-mediated systems throughout the brain and spinal cord including a differential alteration in ectoenzyme activity and ectoenzyme-mediated metabolism of neuropeptides. In this review, Tom Davis and Chris Konkoy suggest that the modulation of ectoenzyme-mediated peptide metabolism represents an additional level at which the concentration of extracellular neuropeptides, and thus peptide-mediated transmission, can be regulated.
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