EFFECT OF CARBOXYPEPTIDASE INHIBITION ON THE INVIVO AND INVITRO PHARMACOLOGICAL PROPERTIES OF MORPHINE AND ENKEPHALINS

Analgesia by enkephalins is of short duration probably due to rapid degradation by peptidases. An attempt was made to evaluate the action of either d-phenylalanine or β-phenylpropionic acid, two in vitro inhibitors of carboxypeptidase A activity, on the extent and duration of the analgesia elicited by exogenous methionine-enkephalin (Met-Enk) as well as by endogenously released peptides. The effect of d-phenylalanine added to the bath fluid on the inhibition of electrically stimulated guinea pig ileum contraction by methionine-enkephalin and morphine was also examined. In the present experiments, carboxypeptidase A inhibition did not affect per se either the pain threshold of mice or the electrically evoked contraction of guinea pig ileum, but it significantly increased the effect of enkephalins. © 1979.