Characterization of neurotransmitters and dopamine attenuation of inducible nitric oxide synthase in glioma cells.

Inducible nitric oxide synthase (iNOS) plays a significant role in the pathology of central nervous system diseases. Inducible NOS expression is regulated by intracellular adenosine 3',5'-cyclic monophosphate (cAMP) signaling, and astrocytes contain both iNOS and adenylate cyclase-coupled neurotransmitter receptors. The data obtained from the present study indicated that acetylcholine, lambda-amino-n-butyric acid, glutamate, quinolinic acid, N-methyl-D-aspartate and aspartate have no effect on NO(2)(-) production in C6 glioma cells stimulated by lipopolysaccharide and interferon-gamma. However, dopamine (DA) caused inhibition of NO(2)(-) production and iNOS transcription. The effects of DA were not due to homovanillic acid/3,4-dihydroxyphenylacetic acid, the autoxidative products superoxide (O(2)(-))/hydrogen peroxide (H(2)O(2)) or direct reactions with NO(2)(-). Forskolin, adenylate cyclase activator, dose-dependently reduced NO(2)(-). Meanwhile, (+/-) SKF-38393 D(1) receptor agonist attenuated iNOS in a similar fashion to DA. In addition, the results indicated that DA attenuation of iNOS was significantly impeded by the adenylate cyclase inhibitor MDL-12,330A, the D(1) antagonist SCH-23390, the beta2 adrenergic receptor antagonist ICI-118,551 and the beta1 adrenergic receptor antagonist atenolol. In conclusion, it appears that DA attenuates iNOS through a D(1), beta1 and beta2 adrenergic receptor-linked adenylate cyclase-mediated cAMP cascade.