Protein kinase C inhibitor chelerythrine attenuates the morphine-induced excitatory amino acid release and reduction of the antinociceptive effect of morphine in rats injected intrathecally with pertussis toxin

Gong-Jhe Wu, Zhi Hong Wen, Yi Chen Chang, San Nan Yang, Pao Luh Tao, Chih Shung Wong

研究成果: 雜誌貢獻文章同行評審

5 引文 斯高帕斯(Scopus)

摘要

Neuropathic pain syndromes respond poorly to opioid treatment. In our previous studies, we found that intrathecal (i.t.) injection of pertussis toxin (PTX) produces thermal hyperalgesia, which is poorly responsive to morphine and is accompanied by an increase in cerebrospinal fluid (CSF) levels of excitatory amino acids (EAAs) and protein kinase C (PKC) activation. In the present study, rats were implanted with an i.t. catheter for drug injection and a microdialysis probe for CSF dialysate collection. On the fourth day after injection of PTX (2 μg, i.t.), there was a significant reduction in the antinociceptive effect of morphine (10 μg, i.t.) which was accompanied by an increase in levels of EAAs. Pretreatment with the PKC inhibitor, chelerythrine (25 μg, i.t.) one hour before morphine injection markedly inhibited both effects. These results suggest that, in PTX-treated rats, PKC plays an important role in inhibiting the morphine-induced spinal EAA release, which might be related to the reduced antinociceptive effect of morphine.

原文英語
頁(從 - 到)1801-1807
頁數7
期刊Life Sciences
78
發行號16
DOIs
出版狀態已發佈 - 3月 13 2006
對外發佈

ASJC Scopus subject areas

  • 生物化學、遺傳與分子生物學 (全部)
  • 藥理學、毒理學和藥劑學 (全部)

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