MODULATION OF LIPOPOLYSACCHARIDE-INDUCED TUMOR-NECROSIS-FACTOR-ALPHA AND NITRIC-OXIDE PRODUCTION BY DOPAMINE-RECEPTOR AGONISTS AND ANTAGONISTS IN MICE

The effects of various agonists and antagonists of dopamine D-1 and D- 2 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, agoni sts of dopamine D-2 receptors caused a blunting of both the TNF-alpha and NO responses to LPS injected intraperitoneally. Sulpiride, an anta gonist of dopamine D-2 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 antag onist of dopamine D-1 receptors did not alter LPS-induced TNF-alpha pr oduction, but inhibited LPS-induced NO production. These results indic ate that while the D-2 subtype of dopamine receptors is involved in th e modulation of both LPS-induced TNF-alpha and NO production, dopamine D-1 receptors only regulate the production of NO. Since several drugs possess effect on dopamine D-2 receptors, the present observations ma y be of clinical relevance.