Inhibitory effects of the analgesic neuropeptides kyotorphin and neo-kyotorphin on enkephalin-degrading enzymes from monkey brain.
The inhibitory effects of the analgesic neuropeptides kyotorphin (Tyr-Arg) and neo-kyotorphin (Thr-Ser-Lys-Tyr-Arg) on enkephalin-degrading enzymes were studied. The enzyme used were aminopeptidase (AP), dipeptidyl aminopeptidase (DPP), enkephalinase-A (ENK-A), and angiotensin-converting enzyme (ACE), which were prepared from the monkey brain membrane fraction. Kyotorphin inhibited only DPP (IC50, 18 microM), and the mode of inhibition was non-competitive (Ki, 6 microM). Neo-kyotorphin inhibited AP, DPP, and ACE with IC50 values of 131, 306, and 200 microM, respectively, but the inhibition of the enzyme activities were not effective. The selective inhibition by kyotorphin suggested that kyotorphin might protect the released Met-enkephalin against enzymatic degradation by DPP. Thus, kyotorphin may not only induce the release of Met-enkephalin but also stabilize the released neuropeptide.
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000700:Analgesics / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001921:Brain / Q000201:enzymology*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D010450:Endopeptidases; D004723:Endorphins / Q000494:pharmacology*; D007700:Kinetics; D008252:Macaca fascicularis; D015260:Neprilysin; D011480:Protease Inhibitors
D000700:Analgesics; D000806:Angiotensin-Converting Enzyme Inhibitors; D004723:Endorphins; D011480:Protease Inhibitors; C019448:kyotorphin; C036450:neo-kyotorphin; D010450:Endopeptidases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D015260:Neprilysin