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.
Davis
T P
TP
Porreca
F
F
Burks
T F
TF
Dray
A
A
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D017450:Receptors, Opioid, mu; D001743:Urinary Bladder / Q000187:drug effects
D004745:Enkephalins; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C029992:proenkephalin; D004744:Enkephalin, Methionine; C026771:BAM 12P; C028837:BAM 22P; C039933:peptide E (adrenal medulla)