[Study of a new endogenous inhibitor of enkephalin-degrading enzymes; pharmacological function and metabolism of spinorphin].
Spinorphin, a potent inhibitor of enkephalin degrading enzyme isolated from the bovine spinal cord, produces a dose-related inhibition of electrically evoked contractions of both MVD (mouse vas deferens) and GPI (guinea-pig ileum). Analgesic activity of Spinorphin was evaluated by the tail pinch method. The intraventricularly injected Spinorphin produced antinociceptive effect in a dose-dependent manner, in dose of 50-200 micrograms.mouse-1. Most Spinorphin was degraded when incubated in the spinal cord for 24 hs. However, approximately 86% of the Spinorphin was intact on HPLC when incubated with probestin, which is an inhibitor of aminopeptidase-M. Spinorphin has a high inhibitory activity against enkephalin degrading enzymes when compared to the various hydrolysis products. In conclusion, the most important structure for enkephalin inhibitory activity in Spinorphin. It is suggested that Spinorphin acts as a neuromodulator of enkephalin metabolism in the spinal cord.
Nishimura
K
K
Department of Anesthesiology, Juntendo University, School of Medicine, Tokyo.
Ueki
M
M
Kaneto
H
H
Hazato
T
T
D000818:Animals; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology*; D013116:Spinal Cord / Q000378:metabolism
D009842:Oligopeptides; C082392:spinorphin; D015260:Neprilysin