1. Histamine influences body temperature by acting at H1 and H3 receptors on distinct populations of preoptic neurons.
- Author
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Lundius EG, Sanchez-Alavez M, Ghochani Y, Klaus J, and Tabarean IV
- Subjects
- 6-Cyano-7-nitroquinoxaline-2,3-dione pharmacology, Action Potentials drug effects, Animals, Animals, Newborn, Calcium metabolism, Cells, Cultured, Enzyme Inhibitors pharmacology, Excitatory Amino Acid Antagonists pharmacology, Excitatory Postsynaptic Potentials drug effects, Gene Expression Regulation drug effects, Glutamate Decarboxylase genetics, Glutamate Decarboxylase metabolism, Glutamic Acid metabolism, Green Fluorescent Proteins genetics, Histamine Agonists pharmacology, Histamine Antagonists pharmacology, In Vitro Techniques, Mice, Mice, Transgenic, Motor Activity drug effects, Motor Activity physiology, Patch-Clamp Techniques, Receptors, Histamine H1 drug effects, Receptors, Histamine H3 drug effects, Signal Transduction drug effects, Signal Transduction physiology, Sodium Channel Blockers pharmacology, Telemetry methods, Tetrodotoxin pharmacology, Type C Phospholipases metabolism, gamma-Aminobutyric Acid metabolism, Body Temperature drug effects, Histamine pharmacology, Neurons drug effects, Preoptic Area cytology, Receptors, Histamine H1 metabolism, Receptors, Histamine H3 metabolism
- Abstract
The preoptic area/anterior hypothalamus, a region that contains neurons that control thermoregulation, is the main locus at which histamine affects body temperature. Here we report that histamine reduced the spontaneous firing rate of GABAergic preoptic neurons by activating H3 subtype histamine receptors. This effect involved a decrease in the level of phosphorylation of the extracellular signal-regulated kinase and was not dependent on synaptic activity. Furthermore, a population of non-GABAergic neurons was depolarized, and their firing rate was enhanced by histamine acting at H1 subtype receptors. In our experiments, activation of the H1R receptors was linked to the PLC pathway and Ca(2+) release from intracellular stores. This depolarization persisted in TTX or when fast synaptic potentials were blocked, indicating that it represents a postsynaptic effect. Single-cell reverse transcription-PCR analysis revealed expression of H3 receptors in a population of GABAergic neurons, while H1 receptors were expressed in non-GABAergic cells. Histamine applied in the median preoptic nucleus induced a robust, long-lasting hyperthermia effect that was mimicked by either H1 or H3 histamine receptor subtype-specific agonists. Our data indicate that histamine modulates the core body temperature by acting at two distinct populations of preoptic neurons that express H1 and H3 receptor subtypes, respectively.
- Published
- 2010
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