Effect of bestatin and thiorphan on (Met super(5))enkephalin-Arg super(6)-Phe super(7)-induced analgesia

The authors investigated the effect of bastatin, a specific inhibitor of aminopeptidase and thiorphan, a specific inhibitor of enkephalinase A, on the analgesic effect induced by the intracerebral injection of heptapeptide (Met super(5))enkephalin-Arg super(6)-Phe super(7) (MEAP) in cannulated rats. In contrast with the results obtained when (Met super(5))enkephalin (ME) was used, bestatin clearly potentiated the analgesic effect of MEAP, but thiorphan was totally ineffective. The observations indicate that the predominant inactivating mechanism for MEAP is the action of an aminopeptidase whereas this enzyme seems to be little involved in the catabolism of ME. The existence of two different catabolic pathways for MEAP and ME suggest that MEAP may act not only as a precursor of ME but also as an independent neuromodulator.