The effects of phorbol 12-myristate 13-acetate, cholera toxin, prostaglandin E2 and norepinephrine on inducible nitric oxide synthase activation induced by lipopolysaccharide in C6 cells.

Nitric oxide (NO) plays a significant role in the pathophysiology of the central nervous system including inflammatory, ischemic and traumatic injuries. We demonstrated the possible involvement of protein kinase C (PKC) as well as protein kinase A (PKA) in the regulation of NO synthesis induced by lipopolysaccharide (LPS) treatment. In this study, the role of phorbol 12-myristate 13-acetate (PMA), cholera toxin (CTX), pertussis toxin (PTX), prostaglandin E(2) (PGE(2)) and norepinephrine (NE) in the regulation of NO synthesis was examined in C6 glioma cells. Stimulation with LPS (1 microg/ml) evoked increases in NO production in C6 glioma cells. LPS-induced NO production was enhanced by pretreatment with PMA, CTX and PGE(2). PTX pretreatment had no effect on NO production induced by LPS. In addition, NE inhibited NO production elicited by LPS treatment. These results suggest that NO production induced by LPS in C6 glioma cells is regulated by several kinds of pathways in which CTX-specific G protein, PKC, prostanoid EP(4) receptor and adrenergic receptor may play important roles.