1993 Fiscal Year Final Research Report Summary
A New Pain relief substance in spinal cord ; Parmacological Function and Metabolism of Spinorphin
| Project/Area Number |
04671424
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | The TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE |
|---|
Principal Investigator |
HAZATO Tadahiko The TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE Cancer Therapeutics, Principal Scientist, 化学療法研究部門, 研究員 (60109949)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAYA Keiji JUNTENDO UNIVERSITY SCHOOL OF MEDICINE, Anesthegiology, Professor, 医学部・麻酔科, 教授 (20124969)
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Keywords | Spinorphin / Spinal Cord / Pain Relief Substance / Opioid / Endogenous Substance / Inhibitor / Enkephalin-Degrading Enzymes |
|---|
| Research Abstract |
In this study, We isolated a potent inhibitor for enkephalin-degrading enzymes from the bovine spinal cord, and determined its amino-acid sequence, pharmacological function and metabolism. This new substance is composed of heptapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr), and has been named by us "Sinorphin". The inhibitory activity (IC_<50>) of this new substance toward enkephalin-degrading enzymes, purified frome monkey brain, was found to be 3.3ug/ml against aminopeptidase, 1.4ug/ml against dipeptidyl aminopeptidase, 2.4ug/ml against angiotensin-converting enzyme, and 10ug/ml against enkephalinase. This substance did not show inhibitory activity toward enkephalins purified kidney and blood. Spinorphin produces a dose-related inhibition of electrically evoked concentrations of both MVD(mouse vas deferens) and GPI(guinea-pig ileum). The intracisternally injected Spinorphin also produced a nalgesic effects in a dose-dependent manner, in dose of 100-200 nmol/mouse.
The analgesic effect reached the maximum within 5 minand disapeard after 15-60min. These effects could be completely antagonised by naloxone. Most Spinorphin was degraded when incubated in the human spinal cord for 24hr. 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 opioid activity is Spinorphin. It is suggested that Spinorphin acts as a neuromodulator of enkephalin metabolism in the spinal cord.
|
