Opiate receptor antagonism by L-prolyl-L-leucyl-glycinamide, MIF-I.
Chronic administration of 1-prolyl-l-leucyl-glycinamide (MIF-I) to mice slightly reduced morphine's antinociceptive activity in the hot-plate test and modified the biphasic motor activity response to morphine. MIF-I antagonized the initial depression of activity and potentiated the increased motor activity phase. Chronic treatment of rats with MIF-I prevented morphine's antinociceptive activity in the tail flick tests. MIF-I partly antagonized the inhibition by morphine of the coaxially stimulated guinea-pig ileum preparation. The inhibition of the ileum produced by ethylketocyclazocine was weakly antagonized by MIF-I. In contrast, MIF-I had no effect on the inhibition of the stimulated mouse vas deferens produced by Leu-enkephalin. The findings show that MIF-I weakly and selectively inhibits mu-type opiate receptors which suggests that MIF-I could be an endogenous inhibitor of opiate receptors.
D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004743:Enkephalin, Leucine; D004745:Enkephalins / Q000494:pharmacology; D016314:Ethylketocyclazocine; D005260:Female; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D010146:Pain / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects
D004745:Enkephalins; D011957:Receptors, Opioid; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D009020:Morphine; D009075:MSH Release-Inhibiting Hormone; D003496:Cyclazocine