K Nishimura

Juntendo University, Edo, Tōkyō, Japan

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Publications (5)2.41 Total impact

  • K Nishimura, M Ueki, H Kaneto, T Hazato
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    ABSTRACT: 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.
    Masui. The Japanese journal of anesthesiology 12/1993; 42(11):1663-70.
  • K Nishimura, T Hazato
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    ABSTRACT: We have isolated a potent inhibitor of enkephalin-degrading enzymes from the bovine spinal cord, and determined its amino-acid sequence and inhibitory activity against enkephalin-degrading enzymes. This new substance, isolated and identified from the bovine spinal cord, is composed of a heptapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr). The inhibitory activity (IC50) of this new substance against enkephalin-degrading enzymes, purified from monkey brain, are 3.3 micrograms.ml-1 against aminopeptidase, 1.4 microgram.ml-1 against dipeptidyl aminopeptidase, 2.4 micrograms.ml-1 against angiotensin converting enzyme, and 10 micrograms.ml-1 against enkephalinase. This new substance showed no inhibitory activity against enkephalin-degrading enzymes purified from kidney, blood, etc. According to the above results, this substance is thought to be a new neuromodulator derived from the spinal cord. Because it was derived from the spinal cord, we have named it "Spinorphin". The discovery in the bovine spinal cord of endogenous heptapeptide, Spinorphin, with inhibitory activity on enkephalin-degrading enzymes raises a number of pertinent questions which cannot be adequately dealt with in this study. It will now be possible, however, to test the very hypothesis that this new peptide act as neurotransmitters or neuromodulators at synaptic junctions.
    Masui. The Japanese journal of anesthesiology 11/1993; 42(10):1497-503.
  • K Nishimura, T Hazato
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    ABSTRACT: We isolated a potent inhibitor of enkephalin-degrading enzymes from bovine spinal cord and determined its amino-acid sequence and inhibitory activity toward enkephalin-degrading enzymes. This new substance, designated spinorphin, is composed of a heptapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr). The inhibitory activity (IC50) of this new substance toward enkephalin-degrading enzymes, purified from monkey brain, was found to be 3.3 micrograms/ml against aminopeptidase, 1.4 micrograms/ml against dipeptidyl aminopeptidase, 2.4 micrograms/ml against angiotensin-converting enzyme, and 10 micrograms/ml against enkephalinase. This new substance did not show inhibitory activity toward enkephalin degrading enzymes purified from kidney and blood. Above results suggest that this substance is a new neuromodulator in the spinal cord.
    Biochemical and Biophysical Research Communications 08/1993; 194(2):713-9. · 2.41 Impact Factor
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    ABSTRACT: Kyotorphin is an analgesic neuropeptide isolated from the bovine brain in 1979. Further studies showed that kyotorphin produces an analgesia through an increased release of met-enkephalin in the brain and the spinal cord. We showed that it is also found in the human cerebrospinal fluid and the concentrations of kyotorphin in normal human CSF is 1.19 +/- 0.51 pmol.ml-1. We also found that it is lower in patients with persistent pain (0.24 +/- 0.04 pmol.ml-1). Above results suggest that kyotorphin acts as a putative neuromediator and/or an endogenous pain modulator in the human brain.
    Masui. The Japanese journal of anesthesiology 12/1991; 40(11):1686-90.
  • K Nishimura, T Hazato
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    ABSTRACT: By the use of high performance liquid chromatography and a specific radioimmunoassay method combined with a new dialysis technique, plasma levels of leu-enkephalin were determined in 26 women who had become pregnant normally, some of whom were in 5 to 40 weeks gestation and the others were 3 days postpartum. Leu-enkephalin-like immunoactivity rose during 5-6 weeks gestation (982.0 +/- 388.3pg.ml-1) and 3 days after delivery (594.4 +/- 289.2pg.ml-1). This pattern differed significantly from that of the normal adult control groups (174.9 +/- 75.3pg.ml-1). The concentrations of serum leu-enkephalin during 10-40 weeks of gestation were within normal limits. These results indicate that the serum leu-enkephalin concentrations increase in the early stage of pregnancy. Whereas the physiological mechanism and exact meaning of this change are still unknown, the results strongly suggest that this substance has an important part to play in such physiological functions as pregnancy.
    Masui. The Japanese journal of anesthesiology 08/1989; 38(7):888-90.