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 captopril did not influence the twitch inhibition of met-enkephalin, but bestatin increased the twitch inhibitory potency of met-enkephalin and terminated it in a manner which almost paralleled that of untreated tissue. Transient inhibition of twitch contraction after tetanic stimulation (post-tetanic twitch inhibition) was obtained. Bestatin increased the potency of met-enkephalin and this was terminated within 2 min. Phosphoramidon tended to increase the potency and delayed the termination of post-tetanic twitch inhibition. Bacitracin, thiorphan and captopril did not influence either the potency or the termination of post-tetanic twitch inhibition. Morphine-induced twitch inhibition was not influenced by bacitracin, bestatin or phosphoramidon. These results suggest that bestatin-sensitive aminopeptidase and phosphoramidon-sensitive enkephalinase take part in post-tetanic twitch inhibition, acting in a different mode of action, and have an important role in the termination of the pharmacological action of endogenous opioids (post-tetanic twitch inhibition) in MPLM. This different mode of response of bestatin and phosphoramidon upon post-tetanic twitch inhibition may underlie that aminopeptidase is a more soluble enzyme and enkephalinase is membrane-bound in myenteric plexus-longitudinal muscle (MPLM).
Ozaki
M
M
Department of Toxicology, Niigata College of Pharmacy, Japan.
Miyamoto
Y
Y
Kishioka
S
S
Masuda
Y
Y
Yamamoto
H
H
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004723:Endorphins / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology*; D015244:Thiorphan / Q000494:pharmacology
D004723:Endorphins; D006020:Glycopeptides; D011480:Protease Inhibitors; D001414:Bacitracin; D004744:Enkephalin, Methionine; D009020:Morphine; D002216:Captopril; D015244:Thiorphan; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex; C008890:phosphoramidon