EFFECT OF SOME PEPTIDASE INHIBITORS ON EXOGENOUS AND ENDOGENOUS OPIOID ACTIONS IN GUINEA-PIG ILEUM

Met-enkephalin concentration-dependently and transiently inhibited the ileal twitch contraction and this inhibition gradually recovered with time. Bacitracin, phosphoramidon, thiorphan and captoril did not infl uence the twitch inhibition of met-enkephalin, but bestatin increased the twitch inhibitiory potency of met-enkephalin and terminated it in a manner,which almost paralleled that of untreated tissue. Transient i nhibition of twitch contraction after tetanic stimulation (post-tetani c twitch inhibition) was obtained. Bestatin increased the potency of m et-enkephalin and this was terminated within 2 min. Phosphoramidon ten ded to increase the potency and delayed the termination of post-tetani c twitch inhibition. Bacitracin, thiorphan and captopril did not influ ence either the potency or the termination of post-tetanic twitch inhi bition. Morphine-induced twitch inhibition was not influenced by bacit racin, bestatin or phosphoramidon. These results suggest that bestatin -sensitive aminopeptidase and phosphoramidon-sensitive enkephalinase t ake part in post-tetanic twitch inhibition, acting in a different mode of action, and have an important role in the termination of the pharm acological action of endogenous opioids (post-tetanic twitch inhibitio n) in MPLM. This different mode of response of bestatin and phosphoram idon upon post-tetanic twitch inhibition may underlie that aminopeptid ase is a more soluble enzyme and enkephalinase is membrane-bound in my enteric plexus-longitudinal muscle (MPLM).