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-OMe on the electrically stimulated cholinergic contractions of the longitudinal 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 the contractions to electrical stimulation, the IC50 value being 1.96 +/- 0.06 microM. Naloxone (1-5 microM) did not reverse the H-Gly-Phe-OMe effects. 3. H-Gly-Phe-OMe at single concentrations (1-10 microM) significantly decreased the maximum inhibition produced by cumulatively added (0.1 nM-100 microM) morphine, Met-enkephalin or Leu-enkephalin. The regression lines for the opioids were shifted to the right but not always in a parallel fashion; the IC50 values were higher as compared to the controls 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-enkephalin (9.06 +/- 0.98); the slope of the pA2 plot to morphine was near unity. 5. These data indicated that H-Gly-Phe-OMe exerted predominantly a potent non-competitive opioid antagonistic effect suggesting that short enkephalin fragments containing the Gly-Phe sequence might possess an opioid activity.
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
R
R
Radomirov
N
N
Pencheva
I
I
Stoyneva
L
L
Lazova
D000109:Acetylcholine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D004558:Electric Stimulation; D004743:Enkephalin, Leucine / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*
D004745:Enkephalins; D010446:Peptide Fragments; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D009020:Morphine; D000109:Acetylcholine