Modulation of lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production by dopamine receptor agonists and antagonists in mice.

ABSTRACT

The effects of various agonist and antagonists of dopamine D1 and D2 receptors on lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production was investigated in mice. Pretreatment of animals with bromocryptine or quinpirole, agonists of dopamine D2 receptors caused a blunting of both the TNF-alpha and NO responses to LPS injected intraperitoneally. Sulpiride, an antagonist of dopamine D2 receptors, decreased the LPS-induced TNF-alpha plasma levels in a dose-dependent manner and inhibited the LPS-induced NO production by peritoneal macrophages. Bromocryptine or quinpirole blunted both the TNF-alpha and NO response to LPS. SCH-23390, an antagonist of dopamine D1 receptors did not alter LPS-induced TNF-alpha production, but inhibited LPS-induced NO production. These results indicate that while the D2 subtype of dopamine receptors is involve in the modulation of both LPS-induced TNF-alpha and NO production, dopamine D1 receptors only regulate the production of NO. Since several drugs possess effect on dopamine D2 receptors, the present observations may be of clinical relevance.