OPIOID EFFECTS OF SHORT ENKEPHALIN FRAGMENTS CONTAINING THE GLY-PHE SEQUENCE ON CONTRACTILE RESPONSES OF GUINEA-PIG ILEUM

1. Effects of the fragments H-Gly-Phe-OH, H-Gly-Phe-NH2 or H-Gly-Phe-O Me on the electrically stimulated cholinergic contractions of the long itudinal layer in isolated guinea pig ileum and on the Morphine-, Met- enkephalin- or Leu-enkephalin-induced inhibition of these contractions were analyzed for opioid activity in respect to Gly-Phe sequence. 2. H-Gly-Phe-OH or H-Gly-Phe-NH2 exerted no effects, while H-Gly-Phe-OMe applied cumulatively (1 pM-1 mM), concentration-dependently reduced th e contractions to electrical stimulation, the IC50 value being 1.96 +/ - 0.06 muM. Naloxone (1-5 muM) did not reverse the H-Gly-Phe-OMe effec ts. 3. H-Gly-Phe-OMe at single concentrations (1-10 muM) significantly decreased the maximum inhibition produced by cumulatively added (0.1 nM-100 muM) morphine, Met-enkephalin or Leu-enkephalin. The regression lines for the opioids were shifted to the right but not always in a p arallel fashion; the IC50 values were higher as compared to the contro ls and lower as compared to the IC50 values after naloxone. 4. The pA2 value for H-Gly-Phe-OMe with respect to morphine (6.43 +/- 0.14) did not differ from that to Met-enkephalin (6.68 +/- 0.35) or Leu-enkephal in (90.6 +/- 0.98); the slope of the pA2 plot to morphine was near uni ty. 5. These data indicated that H-Gly-Phe-OMe exerted predominantly a potent non-competitive opioid antagonistic effect suggesting that sho rt enkephalin fragments containing the Gly-Phe sequence might posses a n opioid activity.