Effects of histamine and alpha-fluoromethylhistidine on brain tumor necrosis factor levels in rats.
Besides the role of histamine (HA) as a neurotransmitter, a new concept has emerged presenting HA as an immunomodulator. Several studies have demonstrated interactions among HA, interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF), suggesting a possible bidirectional communication among them. In this study we have investigated the effects of i.p. administrations of HA diphosphate (6 mumol/kg) and alpha-fluoromethylhistidine (FMH; 100 mg/kg) on TNF-alpha levels in the hippocampus, hypothalamus, and posterior hypothalamic region of the rat brain. The concentrations of TNF-alpha at 0 (Control, C) and 30 min after i.p. administration of HA were 0.26 +/- 0.02 pg/mg and 0.32 +/- 0.02 pg/mg in the hippocampus, 0.46 +/- 0.04 pg/mg and 0.09 +/- 0.006 pg/mg (p < 0.01) in the hypothalamus, and 0.47 +/- 0.05 pg/mg and 0.26 +/- 0.05 pg/mg in the posterior hypothalamic region. Three hours after FMH administration, an increase in the hippocampal levels of TNF-alpha was observed (0.43 +/- 0.04 pg/mg; p < 0.01), while in the hypothalamus (0.11 +/- 0.02 pg/mg; p < 0.01) and in the posterior hypothalamic region (0.21 +/- 0.04 pg/mg; p < 0.05) a decrease in TNF-alpha levels was detected. These results suggest that changes in the histaminergic system influence TNF-alpha production in the brain in an area-specific fashion.
Fernández-Novoa
L
L
Department of Biomedical Research, Basic and Clinical Research Center, La Coruña, Spain.
Franco-Maside
A
A
Alvarez
X A
XA
Cacabelos
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R
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008762:Methylhistidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008762:Methylhistidines; D014409:Tumor Necrosis Factor-alpha; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase