항정신병 약물이 Cyclooxygenase-2 유전자 발현과 Prostaglandin E2 농도에 미치는 영향
The Effects of Antipsychotic Drugs on Cyclooxygenase-2 Gene Expression and Prostaglandin E2 Level
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목 적:기왕의 연구에서 prostaglandin이나 prostaglandin 합성효소인 COX-2가 정신분열병의 병인론과의 연관성에 관한 단편적인 제안 및 항정신병 약물들이 prostaglandin이나 COX-2에 영향을 미칠 것이라는 추론이 제기되었다. 본 연구는 항정신병 약물의 진통작용 기전이 prostaglandin 농도나 COX-2 유전자 수준에서 어떠한 영향을 미칠 것이라는 가설에 입각하여 항정신병 약물인 전통적인 항정신병 약물로서 chlorpromazine과 비정형 항정신병 약물로서 clozapine을 이용하여 PGE2 농도와 COX-2 유전자 발현에 미치는 영향을 분자생물학적 방법을 이용하여 알아보고자 하였다.방 법:먼저 P-815 세포를 배양후 실험에 사용할 chlrorpromazine과 clozapine 두가지의 항정신병 약물을 처치후 RT-PCR 방법을 이용하여 COX-2 유전자 발현정도를 분석하고, western blotting 방법을 이용하여 COX-2 단백질의 발현정도를 측정하였다. 그리고 Prostaglandin E2 enzymeimmunoassay(EIA) system(amersham pharmacia biotech, UK)을 이용하여 전체 세포의 PGE2 농도를 측정하였다.
Abstract
Objectives : Cyclooxygenase(COX) is the central enzyme in the biosynthetic pathway to prostaglandins from arachidonic acids. The action mechanism of nonsteroidal anti-inflammatory drugs is through inhibition of COX activity and prostanoid biosynthesis including prostaglandin E2(PGE2). The antipsychotic drugs are known having an analgesic effects, however its mechanisms of action to pain control was not still clearly proved. In the present study, the effects of antipsychotic drugs(chlorpromazine and clozapine) on the production of PGE2 and the expression of COX-2 mRNA and protein in P815 cell line were studied. Methods : For that purpose, the methods of RT-PCR, western blot and prostagalndin E2 enzymeimmunoassay were applied. Results : The results showed that in P815 cells treated with chlorpromazine, the level of COX2 mRNA was significantly decreased compared to the control cells. And total cellular PGE2 levels were significantly decreased after treatment with chlorpromazine and clozapine. Conclusion : These results suggest that antipsychotic drugs have revealed their analgesic effect through the inhibition of COX-2 activity and PGE2 production. And also, these results partly support the excess theory of prostaglandins in the pathogenesis of schizophrenia.