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Eur J Pharmacol. 1985 May 8;111(2):177-83.

The proenkephalin A fragment, peptide E: central processing and CNS activity in vivo.


The proenkephalin A derivative, peptide E, delayed gastrointestinal transit in mice and inhibited the micturition reflex in anesthetized rats after intracerebroventricular (i.c.v.) administration. BAM22P, BAM12P and [Met5]enkephalin, possible processing fragments of peptide E, were also compared in the two test systems. Of these peptides, peptide E and BAM 22P were found to have the greatest potency and activity. Studies in vitro of peptide E metabolism by enzyme homogenates of mouse brain using HPLC techniques revealed that peptide E is bound to the membrane homogenate avidly for an extended period of time. The total formation of BAM22P, BAM12P, [Met5]enkephalin and all other peptide fragments during a 40 min incubation period accounted for only 8% of the total peptide E added to the homogenates. Thus, peptide E, rather than one of its known metabolites, appears to be of primary importance in the initiation of CNS-mediated effects. Further, these effects are probably the result of mu-opioid receptor activation.

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