Characterization of leucine and methionine enkephalin and their interaction with morphine on the guinea pig ileal longitudinal muscle.
Using naloxone as the antagonist, a comparison of pA2 values obtained from the guinea pig ileal longitudinal muscle preparation revealed that both leucine (leu-) enkephalin and methionine (met-) enkephalin can be classified as pure narcotic agonists with pA2 values similar to that of morphine but different from that of nalorphine. In addition, cross tolerance to both met- and leu-enkephal in could be demonstrated on an ileal strip made tolerant to morphine by implantation of morphine pellets to a guinea pig for 72 hours. Pretreatment of a naive muscle strip to three increasing concentrations of leu-enkephalin was found to markedly decrease the IC50 of morphine and to sensitize the ileal strip to naloxone as was evidenced by an increase in the morphine-naloxone pA2 value. Met-enkephalin or morphine pretreatment had no effect on subsequent morphine IC50 determinations but similarly increased the morphine-naloxone pA2 value. These results suggest that although both leu- and met-enkephalin may be classified as pure narcotic agonists, their interaction with morphine on the ileal strip is markedly different. Leu-enkephalin may be an important physiological modulator of narcotic efficacy.
D000818:Animals; D004347:Drug Interactions; D004361:Drug Tolerance; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009269:Nalorphine / Q000494:pharmacology
D004723:Endorphins; D004745:Enkephalins; D009020:Morphine; D009269:Nalorphine