| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
Immunosuppression is one of major side effects of opioid analgesics. However, its definite mechanisms remain to be clarified. To investigate whether changes of gene expression induced by opioid might be involved in the plastic changes of immune system, subtraction PCR and differential screening was performed using cDNAs extracted from cultured human peripheral blood T cells stimulated by 10 μM morphine hydrochloride and vehicle for 12 hours.
As a result, we have picked up 125 and 57 candidates of molecules upregulated and downregulated by morphine, respectively. Upregulation of p53 and its regulator molecules, eukaryotic initiation factor (eIF5A) and syntenin, was confirmed by RT-PCR technique. Damage-specific DNA binding protein 2 (DDB2), which is induced when DNA is damaged by UV, was also proved to be upregulated by morphine. We are now studying the phenomena of the DNA damage and the apoptosis of T cells induced by morphine.
Another project was to analyze the effects of various drugs on hypothalamus-pituitary-adrenal system using a cultured pituitary cell line, AtT20PL cells, stably transfected with proopiomelanocortin (POMC) 5' promoter linked with the luciferase gene. It was concluded that local anesthetics andcalcium channel blockers, nifedipine and verapamil, enhance the CRH-and forskolin-stimulated promoter activity of POMC.
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