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Fever is the widely known hallmark of disease and is induced by the action of the nervous system. It is generally accepted that prostaglandin (PG) E(2) is produced in response to immune signals and then acts on the preoptic area (POA), which triggers the stimulation of the sympathetic system, resulting in the production of fever. Actually, the EP3 subtype(More)
Fever is induced by a neuronal mechanism in the brain. Prostaglandin (PG) E2 acts as a pyrogenic mediator in the preoptic area (POA) probably through the EP3 subtype of PGE receptor expressed on GABAergic neurons, and this PGE2 action triggers neuronal pathways for sympathetic thermogenesis in peripheral effector organs including brown adipose tissue (BAT).(More)
Hydrogen peroxide (H(2)O(2)), which is contained in industrial products, is also generated within cells. H(2)O(2) causes pain but it has not been elucidated how it activates sensory neurons in the pain pathway. Here we show that transient receptor potential ankyrin 1 (TRPA1), expressed by sensory neurons in the pain pathway, is a receptor for H(2)O(2).(More)
TRPM8 is a TRP family cation channel which can be activated by cold stimuli or l-menthol. However, TRPM8 protein localization of nerve terminals in sensory organs remains unknown. Here we generated an antibody against TRPM8 and analyzed TRPM8 protein localization in trigeminal ganglia (TG) and in sensory nerve fibers in the tongue. TRPM8 immunoreactivity(More)
Sympathetic premotor neurons directly control sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column (IML) of the thoracic spinal cord, and many of these premotor neurons are localized in the medulla oblongata. The rostral ventrolateral medulla contains premotor neurons controlling the cardiovascular conditions, whereas rostral(More)
Brain endothelial cells are hypothesized to be the major source of prostaglandin E(2) (PGE(2)) responsible for fever because they express 2 PGE(2)-synthesizing enzymes (cyclooxygenase-2 and microsomal-type PGE synthase) in response to pyrogens. To further validate this hypothesis, we examined in rats whether endothelial expression of these enzymes occurs(More)
Fever is triggered by an elevation of prostaglandin E(2) (PGE(2)) in the brain. However, the mechanism of its elevation remains unanswered. We herein cloned the rat glutathione-dependent microsomal prostaglandin E synthase (mPGES), the terminal enzyme for PGE(2) biosynthesis, and examined its induction in the rat brain after intraperitoneal injection of(More)
TRPM8 and TRPA1, members of the transient receptor potential (TRP) channel family, are candidates for cooling-activated receptors. It is accepted that TRPM8 responds to moderate cooling, although it is controversial whether TRPA1 responds to deep cooling. Here, using Ca(2+) imaging and/or patch-clamp recordings, we examined the thermal sensitivity of(More)
Cyclooxygenase-2 (COX-2), a key enzyme in the biosynthesis of prostaglandins, is induced in brain blood vessels by pyrogens, and its essential role in fever has been hypothesized. In this study, we determined (1) the type of cells that express cyclooxygenase-2 in brain blood vessels of lipopolysaccharide-treated rats, and (2) the precise relationship(More)
All phases of lipopolysaccharide (LPS)-induced fever are mediated by prostaglandin (PG) E2. It is known that the second febrile phase (which starts at approximately 1.5 h post-LPS) and subsequent phases are mediated by PGE2 that originated in endotheliocytes and perivascular cells of the brain. However, the location and phenotypes of the cells that produce(More)