Dopamine and different dopaminergic drugs are widely used in the treatment of several immune-mediated diseases like Parkinson's disease or septic shock.Tumor necrosis factor-α and the free radical nitric oxide (NO) have been implicated in the pathogenesis of these pathophysiologic conditions. In the present study we have therefore investigated the effect of various dopamine receptor agonists and antagonists on the lipopolysaccharide-induced production of tumor necrosis factor-alpha and NO in mice. Pretreatment of animals with bromocryptine or quinpirole, agonists of D2 dopamine receptors caused a blunting of both the tumor necrosis factor-α and NO responses to lipopolysaccharide injected intraperitoneally. Sulpiride, an antagonist of dopamine D2 receptors, decreased the lipopolysaccharide-induced tumor necrosis factor-α plasma levels in a dose-dependent manner and inhibited the lipopolysaccharideinduced nitric oxide production by peritoneal macrophages. Bromocryptine or quinpirole, agonists of Da dopamine receptors, blunted both the tumor necrosis factor-a and NO response to lipopolysaccharide. SCH-23390, an antagonist of dopamine DI receptors did not alter lipopolysaccharide-induced tumor necrosis factor-a production, but inhibited lipopolysaccharide-induced NO production. These results indicate that while the D£ dopamine receptor is involved in the modulation of both lipopolysaccharide-induced tumor necrosis factor-α and NO production. DI dopamine receptors only regulate NO production. As many drugs possess effect on D2 dopamine receptors, our observations may be of clinical relevance.
|Publication status||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology