title: 5-HT2A receptors control body temperature in mice during LPS-induced inflammation via regulation of NO production.
abstract: G protein-coupled 5-HT2A receptors are involved in the regulation of numerous normal and pathological physiological functions. At the same time, its involvement in the regulation of body temperature (Tb) in normal conditions is obscure. Here we study the effect of the 5-HT2A receptor activation or blockade on Tb in sick animals. The experiments were carried out on adult C57BL/6 mouse males. Systemic inflammation and sickness were produced by lipopolysaccharide (LPS, 0.1mg/kg, ip), while the 5-HT2A receptor was stimulated or blocked through the administration of the receptor agonist DOI or antagonist ketanserin (1mg/kg), respectively. LPS, DOI or ketanserin alone produced no effect on Tb. However, administration of LPS together with a peripheral or central ketanserin injection reduced Tb (32.2°C). Ketanserin reversed the LPS-induced expression of inducible NO synthase in the brain. Consequently, an involvement of NO in the mechanism of the hypothermic effect of ketanserin in sick mice was hypothesized. Administration of LPS together with NO synthase inhibitor, l-nitro-arginine methyl ester (60mg/kg, ip) resulted in deep (28.5°C) and prolonged (8h) hypothermia, while administration of l-nitro-arginine methyl ester alone produced no effect on Tb. Thus, 5-HT2A receptors play a key role in Tb control in sick mice. Blockade of this GPCR produces hypothermia in mice with systemic inflammation via attenuation of LPS-induced NO production. These results indicate an unexpected role of 5-HT2A receptors in inflammation and NO production and have a considerable biological impact on understanding the mechanism of animal adaptation to pathogens and parasites. Moreover, adverse side effects of 5-HT2A receptor antagonists in patients with inflammation may be expected.
authors.affiliation: Institute of Physiology and Fundamental Medicine, Siberian Branch of Russian Academy of Medical Sciences, 630117 Novosibirsk, Russia.
authors.forename: Irina P
authors.initials: IP
authors.lastname: Voronova
authors.affiliation: Institute of Physiology and Fundamental Medicine, Siberian Branch of Russian Academy of Medical Sciences, 630117 Novosibirsk, Russia.
authors.forename: Galina M
authors.initials: GM
authors.lastname: Khramova
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kulikova
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Dmitrii V
authors.initials: DV
authors.lastname: Petrovskii
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Bazovkina
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia. Electronic address: akulikov@ngs.ru.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kulikov
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D007249:Inflammation / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D009569:Nitric Oxide; D007650:Ketanserin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
keywords: 5-HT(2A) receptor; Hypothermia; Inducible NO synthase; Ketanserin; Lipopolysaccharide; Mice