Catecholamines inhibit microglial nitric oxide production.

Abstract

Viral infection in the central nervous system can induce nitric oxide production, which serves as a major host defense against viral infection. Under stress, catecholamine secretion is enhanced and immune responses are diminished in animals. Using N9 microglial cells, this study tested the effect of catecholamines on microglial nitric oxide production. Results indicated that each member of the catecholamine family (dopamine, norepinephrine and epinephrine) was a potent inhibitor of the microglial nitric oxide production. In contrast, dopa, the immediate precursor of the catecholamine biosynthesis pathway, was a weak inhibitor, except at very high concentrations. The inhibitory effect of catecholamines was mimicked by an alpha-adrenergic receptor agonist (phenylephrine) and by a beta-adrenergic receptor agonist (isoproterenol), but not by forskolin or analogs of cyclic adenosine monophosphate. Western blot analysis indicated that catecholamines caused a slight decrease in the formation of inducible nitric oxide synthase. These results suggest that catecholamines have the ability to block nitric oxide production by microglia, which could partially explain the impaired immune protection against viral infection in the central nervous system in stressed animals.