PMID: 705020Sep 1, 1978

Characterization of leucine and methionine enkephalin and their interaction with morphine on the guinea pig ileal longitudinal muscle

Research Communications in Chemical Pathology and Pharmacology
J L Vaught, A E Takemori


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.

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