Met5-enkephalin-Arg6-Phe7 inhibition of noradrenaline and acetylcholine release from peripheral organs.
The effect of the opioid heptapeptide Met5-enkephalin-Arg6-Phe7 was measured on the contractions of the longitudinal muscle of the guinea-pig ileum and mouse vas deferens; on release of endogenous and newly synthesized acetylcholine from the longitudinal muscle strip preparation of the guinea-pig ileum and of 3H-noradrenaline from mouse vas deferens. Met5-enkephelin-Arg6-Phe7 depressed the contractions of the longitudinal muscle strip of guinea-pig ileum elicited by low frequency stimulation (IC50 366.5 +/- 71.5 nM). The Ke value of naltrexone against the heptapeptide was found to be 0.50 +/- 0.08 nM. Bestatin prolonged and strongly potentiated the action of the opioid peptide in this tissue while captopril proved to be only slightly effective. Met5-enkephalin-Arg6-Phe7 also inhibited neuroeffector transmission in the mouse vas deferens with an IC50 value of 9.44 +/- 2.24 nM. The Ke value of naltrexone was 6.33 +/- 1.22 nM against the heptapeptide. Met5-enkephalin-Arg6-Phe7 (10(-5) M) failed to affect the low frequency stimulated release of endogenous acetylcholine from the guinea-pig ileum preparation. Addition of either bestatin or captopril with the heptapeptide resulted in a reduction of acetylcholine output. The opioid peptide by itself decreased the release of newly synthesized acetylcholine outflow from this organ. Met5-enkephalin-Arg6-Phe7 also reduced the 3H-noradrenaline outflow from mouse vas deferens and this effect was antagonized by naltrexone. From our data we conclude that Met5-enkephalin-Arg6-Phe7 affects the neural transmission of peripheral autonomically innervated organs by depressing the release of neurotransmitter. In vitro it has enkephalin-like character with a preference for the so called delta receptor interaction.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001369:Axons / Q000187:drug effects; D004558:Electric Stimulation; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D009451:Neuroeffector Junction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D004744:Enkephalin, Methionine; C027511:enkephalin-Met, Arg(6)-Phe(7)-; D000109:Acetylcholine; D009638:Norepinephrine