[Skip to Content]
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
November 1995

The Possible Role of a Central Nervous System Dopaminergic Mechanism in Hepatic c-fos Protein Expression Following Peritoneal Sepsis

Author Affiliations

From the Departments of Surgery (Drs Roy, Chapin, and Barke, Mr Charboneau, and Ms Cain), Pharmacology (Dr Roy), and Food Science and Nutrition (Dr Barke), University of Minnesota, Minneapolis, and the Minneapolis Veterans Administration Hospital.

Arch Surg. 1995;130(11):1209-1216. doi:10.1001/archsurg.1995.01430110067012

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 immunore-active 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.(Arch Surg. 1995;130:1209-1216)

Horgan AF, Mendez MV, O'Riordain DS, Holzheimer RG, Mannick JA, Rodrick ML.  Altered gene transcription after burn injury: results in depressed T-lymphocyte activation . Ann Surg . 1994;220:342-351.Article
Barke RA, Brady PS, Roy S, Charboneau R, Brady LJ.  The possible inhibitory role of the DNA binding protein c-fos in the regulation of gene expression in sepsis . Surgery . 1992;112:412-418.
Brenner DA, O'Hara M, Angel P, Chojkeir M, Karin M.  Prolonged activation of jun and collagenase genes by tumor necrosis factor-α . Nature . 1989;337:661-663.Article
Muegge K, Vila M, Gusella GL, et al.  Interleukin 1 induction of the c-jun promoter . Proc Natl Acad Sci USA . 1993;90:7054-7058.Article
Sawdey MS, Loskutoff DJ.  Regulation of murine type I plasminogen activator inhibitor gene expression in-vivo: tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta . J Clin Invest . 1991;88:1346-1353.Article
Nervlov C, De-Cesare D, Pergola F, et al.  A regulatory element that mediates co-operation between PEA3/AP-1 element and an AP-1 site is required for phorbol ester induction of urokinase enhancer activity in HepG2 hepatoma cells . EMBO J . 1992;11:4573-4582.
Li Y, Jaiswal AK.  Regulation of human NAD(P)H:quinone oxidoreductase gene: role of AP1 binding site contained within human antioxidant response element . J Biol Chem . 1992;267:15097-15104.
Rettori V, Jurcovicova J, McCann SM.  Central action of interleukin-1 in altering the release of TSH, growth hormone, and prolactin in the male rat . J Neurosci Res . 1987;18:179-183.Article
Lyson K, McCann SM.  The effect of interleukin-6 on pituitary hormone release in vivo and in vitro . Neuroendocrinology . 1991;54:262-266.Article
Tong Y, Pelletier G.  Role of dopamine in the regulation of proopiomelanocortin (POMC) mRNA levels in the arcuate nucleus and pituitary gland of the female rat as studied by in-situ hybridization . Mol Brain Res . 1992;15:27-32.Article
Hill AG, Gonzalez J, Rounds JD, Wilmore DW.  Chronic central nervous system exposure to interleukin-1, but not interleukin-6, mediates catabolism in the rat . Surg Forum . 1994;45:38-41.
Barke RA, Roy S, Chapin RB, Charboneau R, Brady PS, Brady LJ.  Sepsis-induced release of interleukin-6 may activate the immediate-early gene program through a hypothalamic-hypophyseal mechanism . Surgery . 1994;116: 141-148.
Zalcman S, Green-Johnson JM, Murray L, et al.  Cytokine specific central monoamine alterations induced by interleukin-1, -2, -6 . Brain Res . 1994;643:40-49.Article
Mohankumar PS, Thyagarajan S, Quadri SK.  Interleukin 1 stimulates the release of dopamine and dihydroxphenylacetic acid from the hypothalamus invivo . Life Sci . 1991;48:925-930.Article
Meador-Woodruff JH.  Update on dopamine receptors . Ann Clin Psychiatry . 1994; 6:79-90.Article
Haloday JW.  Anterior pituitary hormones and critical illness . In: Chernow B, ed. The Pharmacologic Approach to the Critically Ill Patient . Philadelphia, Pa: Williams & Wilkins; 1994:890-900.
Cronin MJ, Thorner MO, Hellman P, Rogol AD.  Bromocriptine inhibits growth hormone release from rat pituitary cells in primary culture . Proc Soc Exp Biol Med . 1984;175:191-195.Article
Honegger J, Spagnoli A, Durso R, et al.  Interleukin-1β modulates the acute release of growth hormone releasing hormone and somatostatin from rat hypothalamus in-vitro, whereas tumor necrosis factor and interleukin-6 have no effect . Endocrinology . 1991;129:1275-1282.Article
Grace AA, Bunney BS.  Induction of depolarization block in midbrain dopamine neurons by repeated administration of haloperidol: analysis using in-vivo intracellular recording . J Pharm Exp Ther . 1986;238:1092-1099.
Jaber M, Tison F, Fournier MC, Bloch B.  Differential influence of haloperidol and sulpiride on dopamine receptors and peptide mRNA levels in the rat striaturn and pituitary . Mol Brain Res . 1994;23:14-20.Article
Baldessarini RJ, Campbell A, Ben-Jonathan N, Ellingboe J, Zong R, Neumeyer JL.  Effects of apomorphine isomers on rat prolactin . Neurosci Lett . 1994;176: 269-271.Article
D'Eramo JL, Somoza GM, Kertesz E, Libertun C.  Baclofen, a GABA derivative, inhibits stress-induced prolactin release in the rat . Eur J Pharmacol . 1986; 120:81-85.Article
Khilnani P, Munoz R, Salem M Gelb C, Todres ID, Chernow B.  Hormonal responses to surgical stress in children . J Pediatr Surg . 1993;28:1-4.Article
Abu-Jayyab A, Mahgoub A.  Role of Na+/K+-stimulated adenosine triphosphate in the action of dopaminerigic-D2 receptors of the liver in rats . Biosci Rep . 1987;7:839-842.Article