The effect of enkephalin and enkephalin analogs on the guinea-pig ileum and rat brain opilate receptor

Abstract

We have synthesized the two naturally occurring enkephalins (Methionine-Enkephalin and Leucine-Enkephalin) as well as four other analogs (Methinonine-Enkephalin amide, S-Benzyl sulphonium analog of Methionine-Enkephalin, 3-Benzyl-tyrosine analog of Methionine-Enkephalin and 3-Benzyl-tyrosine analog of Leucine-Enkephalin) in order to study their relative potency and their inactivation of different tissues. Morphine-like activity of the peptides was determined by measuring their inhibitory effect in the guinea-pig ileum and their interaction with the brain opiate receptor; the order of affinity of the three most active peptides (Methionine-Enkephalin amide greater than Methionine-Enkephalin greater than Leucine-Enkephalin) for the rat brain opiate receptor was found to be the same in the guinea-pig ileum. The rate of inactivation of the peptides was also studied in the guinea-pig ileum and in the rat brain membrane preparation. Methionine-Enkephalin amide was relatively more resistant to the ileum peptidases than the other peptides, but was destroyed at the same rate by brain membranes; this variation in inactivation of Methionine-Enkephalin amide probably indicates the presence of differnet peptidases in each tissue preparation.