The possible role of a central nervous system dopaminergic mechanism in hepatic c-fos protein expression following peritoneal sepsis.
OBJECTIVE
To investigate the hypothesis that a central dopaminergic mechanism may regulate hepatic c-fos and c-jun gene expression following peritoneal sepsis.


METHODS
First, dopamine or vehicle was instilled into a stereotaxically placed intracerebral-ventricular (ICV) cannula with or without D1 (SCH 23390) or D2 (haloperidol) antagonist pretreatment in a rat model, and the effect on hepatic c-fos or c-jun protein expression was investigated. Second, we investigated the effect of haloperidol and vehicle treatment following cecal ligation and puncture (CLP)-induced sepsis with respect to hepatic c-fos protein expression, c-jun protein expression, and survival.


RESULTS
Intracerebral-ventricular dopamine treatment increased hepatic c-fos immunoreactive protein but had no effect on hepatic c-jun immunoreactive protein expression. Pretreatment with SCH 23390 inhibited ICV dopamine treatment-induced hepatic c-fos immunoreactive protein expression. Haloperidol pretreatment synergized with ICV dopamine treatment to overexpress hepatic c-fos protein. Haloperidol treatment significantly increased CLP-induced hepatic c-fos and c-jun protein expression and improved survival following CLP.


CONCLUSIONS
Hepatic c-fos protein expression may be regulated, in part, by a central nervous system-mediated dopaminergic D1 receptor mechanism. Treatment with the D2 receptor antagonist, haloperidol, increases sepsis-induced hepatic c-fos and c-jun protein expression and improves survival following peritoneal contamination.
D000818:Animals; D001921:Brain / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D016762:Genes, fos / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*; D018805:Sepsis / Q000378:metabolism*
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D004298:Dopamine