The effect of enkephalin and enkephalin analogs on the guinea-pig ileum and rat brain opilate receptor.
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.
D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum; D009130:Muscle, Smooth / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects*
D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid