| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Outline of Final Research Achievements |
The purpose of the present study was to evaluate antinociceptive potential and toxicity with administration of Dyn under pretreatment with a mixture of amastatin (A), captopril (C), and phosphoramidon (P), and/or Dyn-converting enzyme inhibitor (p-hydroxymercuribenzoate; PHMB). MALDI-TOF-MS analysis identified Dyn A (1-6) and Dyn A (1-10) fragments as products following incubation of Dyn A (1-17) with membrane preparation of rat midbrain with a mixture of the three PIs. Pretreatment with a mixture of the three PIs produced an approximately 30-fold augmentation in antinociception induced by low-dose administration of Dyn A. Dyn-induced antinociception and toxicity under pretreatment with various combinations of the three PIs and PHMB was greater than that with a mixture of the three PIs alone. These findings suggest that administration of a mixture of the three PIs increases Dyn A-induced antinociception under physiological conditions without toxicity.
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