Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat

<p>Abstract</p> <p>Background</p> <p>Kinins are mediators of pain and inflammation. Their role in thermoregulation is, however, unknown despite the fact the B1 receptor (B1R) was found implicated in lipopolysaccharide (LPS)-induced fever. The aim of this study was to in...

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Main Authors: Talbot Sébastien, De Brito Gariépy Helaine, Saint-Denis Julien, Couture Réjean
Format: Article
Language:English
Published: BMC 2012-09-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:http://www.jneuroinflammation.com/content/9/1/214
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author Talbot Sébastien
De Brito Gariépy Helaine
Saint-Denis Julien
Couture Réjean
author_facet Talbot Sébastien
De Brito Gariépy Helaine
Saint-Denis Julien
Couture Réjean
author_sort Talbot Sébastien
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Kinins are mediators of pain and inflammation. Their role in thermoregulation is, however, unknown despite the fact the B1 receptor (B1R) was found implicated in lipopolysaccharide (LPS)-induced fever. The aim of this study was to investigate the mechanism by which peripheral B1R affects body core temperature in a rat model known to show up-regulated levels of B1R.</p> <p>Methods</p> <p>Male Sprague–Dawley rats received streptozotocin (STZ, 65 mg/kg; i.p.) to enhance B1R expression. Control rats received the vehicle only. One week later, rectal temperature was measured in awake rats after i.p. injection of increasing doses (0.01 to 5 mg/kg) of des-Arg<sup>9</sup>-Bradykinin (BK) and Sar-[D-Phe<sup>8</sup>]des-Arg<sup>9</sup>-BK (B1R agonists) or BK (B2R agonist). The mechanism of B1R-induced hyperthermia was addressed using specific inhibitors and in rats subjected to subdiaphragmatic vagal nerve ligation. B1R mRNA level was measured by quantitative Real Time-polymerase chain reaction (qRT-PCR) and B1R was localized by confocal microscopy.</p> <p>Results</p> <p>B1R agonists (0.1 to 5 mg/kg) showed transient (5- to 30-minute) and dose-dependent increases of rectal temperature (+1.5°C) in STZ-treated rats, but not in control rats. BK caused no effect in STZ and control rats. In STZ-treated rats, B1R agonist-induced hyperthermia was blocked by antagonists/inhibitors of B1R (SSR240612), cyclooxygenase-2 (COX-2) (niflumic acid) and nitric oxide synthase (NOS) (L-NAME), and after vagal nerve ligation. In contrast, COX-1 inhibition (indomethacin) had no effect on B1R agonist-induced hyperthermia. In STZ-treated rats, B1R mRNA was significantly increased in the hypothalamus and the vagus nerve where it was co-localized with calcitonin-gene-related peptide in sensory C-fibers.</p> <p>Conclusion</p> <p>B1R, which is induced in inflammatory diseases, could contribute to hyperthermia through a vagal sensory mechanism involving prostaglandins (via COX-2) and nitric oxide.</p>
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spelling doaj.art-6f2aad77b315444f99bf01bd55fce87e2022-12-21T23:16:07ZengBMCJournal of Neuroinflammation1742-20942012-09-019121410.1186/1742-2094-9-214Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the ratTalbot SébastienDe Brito Gariépy HelaineSaint-Denis JulienCouture Réjean<p>Abstract</p> <p>Background</p> <p>Kinins are mediators of pain and inflammation. Their role in thermoregulation is, however, unknown despite the fact the B1 receptor (B1R) was found implicated in lipopolysaccharide (LPS)-induced fever. The aim of this study was to investigate the mechanism by which peripheral B1R affects body core temperature in a rat model known to show up-regulated levels of B1R.</p> <p>Methods</p> <p>Male Sprague–Dawley rats received streptozotocin (STZ, 65 mg/kg; i.p.) to enhance B1R expression. Control rats received the vehicle only. One week later, rectal temperature was measured in awake rats after i.p. injection of increasing doses (0.01 to 5 mg/kg) of des-Arg<sup>9</sup>-Bradykinin (BK) and Sar-[D-Phe<sup>8</sup>]des-Arg<sup>9</sup>-BK (B1R agonists) or BK (B2R agonist). The mechanism of B1R-induced hyperthermia was addressed using specific inhibitors and in rats subjected to subdiaphragmatic vagal nerve ligation. B1R mRNA level was measured by quantitative Real Time-polymerase chain reaction (qRT-PCR) and B1R was localized by confocal microscopy.</p> <p>Results</p> <p>B1R agonists (0.1 to 5 mg/kg) showed transient (5- to 30-minute) and dose-dependent increases of rectal temperature (+1.5°C) in STZ-treated rats, but not in control rats. BK caused no effect in STZ and control rats. In STZ-treated rats, B1R agonist-induced hyperthermia was blocked by antagonists/inhibitors of B1R (SSR240612), cyclooxygenase-2 (COX-2) (niflumic acid) and nitric oxide synthase (NOS) (L-NAME), and after vagal nerve ligation. In contrast, COX-1 inhibition (indomethacin) had no effect on B1R agonist-induced hyperthermia. In STZ-treated rats, B1R mRNA was significantly increased in the hypothalamus and the vagus nerve where it was co-localized with calcitonin-gene-related peptide in sensory C-fibers.</p> <p>Conclusion</p> <p>B1R, which is induced in inflammatory diseases, could contribute to hyperthermia through a vagal sensory mechanism involving prostaglandins (via COX-2) and nitric oxide.</p>http://www.jneuroinflammation.com/content/9/1/214Kinin B1 receptorDiabetesHyperthermiaInflammationBradykininNOSensory C-fibersThermoregulation
spellingShingle Talbot Sébastien
De Brito Gariépy Helaine
Saint-Denis Julien
Couture Réjean
Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat
Journal of Neuroinflammation
Kinin B1 receptor
Diabetes
Hyperthermia
Inflammation
Bradykinin
NO
Sensory C-fibers
Thermoregulation
title Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat
title_full Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat
title_fullStr Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat
title_full_unstemmed Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat
title_short Activation of kinin B1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat
title_sort activation of kinin b1 receptor evokes hyperthermia through a vagal sensory mechanism in the rat
topic Kinin B1 receptor
Diabetes
Hyperthermia
Inflammation
Bradykinin
NO
Sensory C-fibers
Thermoregulation
url http://www.jneuroinflammation.com/content/9/1/214
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AT saintdenisjulien activationofkininb1receptorevokeshyperthermiathroughavagalsensorymechanismintherat
AT couturerejean activationofkininb1receptorevokeshyperthermiathroughavagalsensorymechanismintherat