title: The sympathetic nervous system is controlled by transient receptor potential vanilloid 1 in the regulation of body temperature.
abstract: Transient receptor potential vanilloid 1 (TRPV1) is involved in sensory nerve nociceptive signaling. Recently, it has been discovered that TRPV1 receptors also regulate basal body temperature in multiple species from mice to humans. In the present study, we investigated whether TRPV1 modulates basal sympathetic nervous system (SNS) activity. C57BL6/J wild-type (WT) mice and TRPV1 knockout (KO) mice were implanted with radiotelemetry probes for measurement of core body temperature. AMG9810 (50 mg/kg) or vehicle (2% DMSO/5% Tween 80/10 ml/kg saline) was injected intraperitoneally. Adrenoceptor antagonists or vehicle (5 ml/kg saline) was injected subcutaneously. In WT mice, the TRPV1 antagonist, AMG9810, caused significant hyperthermia, associated with increased noradrenaline concentrations in brown adipose tissue. The hyperthermia was significantly attenuated by the β-adrenoceptor antagonist propranolol, the mixed α-/β-adrenoceptor antagonist labetalol, and the α1-adrenoceptor antagonist prazosin. TRPV1 KO mice have a normal basal body temperature, indicative of developmental compensation. d-Amphetamine (potent sympathomimetic) caused hyperthermia in WT mice, which was reduced in TRPV1 KO mice, suggesting a decreased sympathetic drive in KOs. This study provides new evidence that TRPV1 controls thermoregulation upstream of the SNS, providing a potential therapeutic target for sympathetic hyperactivity thermoregulatory disorders.
authors.affiliation: *Institute of Pharmaceutical Science and British Heart Foundation Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, King's College London, London, United Kingdom.
authors.forename: Khadija M
authors.initials: KM
authors.lastname: Alawi
authors.affiliation: *Institute of Pharmaceutical Science and British Heart Foundation Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, King's College London, London, United Kingdom.
authors.forename: Aisah A
authors.initials: AA
authors.lastname: Aubdool
authors.affiliation: *Institute of Pharmaceutical Science and British Heart Foundation Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, King's College London, London, United Kingdom.
authors.forename: Lihuan
authors.initials: L
authors.lastname: Liang
authors.affiliation: *Institute of Pharmaceutical Science and British Heart Foundation Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, King's College London, London, United Kingdom.
authors.forename: Elena
authors.initials: E
authors.lastname: Wilde
authors.affiliation: *Institute of Pharmaceutical Science and British Heart Foundation Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, King's College London, London, United Kingdom.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Vepa
authors.affiliation: *Institute of Pharmaceutical Science and British Heart Foundation Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, King's College London, London, United Kingdom.
authors.forename: Maria-Paraskevi
authors.initials: MP
authors.lastname: Psefteli
authors.affiliation: *Institute of Pharmaceutical Science and British Heart Foundation Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, King's College London, London, United Kingdom.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Brain
authors.affiliation: *Institute of Pharmaceutical Science and British Heart Foundation Cardiovascular Centre of Excellence and Centre of Integrative Biomedicine, Cardiovascular Division, King's College London, London, United Kingdom julie.keeble@kcl.ac.uk.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Keeble
mesh_terms: D000178:Acrylamides / Q000008:administration & dosage / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000235:genetics / Q000502:physiology*; D001833:Body Temperature Regulation / Q000235:genetics / Q000502:physiology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology; D005334:Fever / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007741:Labetalol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000502:physiology*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D013686:Telemetry / Q000379:methods
chemical_list: C500530:3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide; D000178:Acrylamides; D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D011433:Propranolol; D007741:Labetalol; D011224:Prazosin
keywords: TRPV1; brown adipose tissue; thermogenesis