title: Brain kinin B1 receptor is upregulated by the oxidative stress and its activation leads to stereotypic nociceptive behavior in insulin-resistant rats.
abstract: Kinin B1 receptor (B1R) is virtually absent under physiological condition, yet it is highly expressed in models of diabetes mellitus. This study aims at determining: (1) whether B1R is induced in the brain of insulin-resistant rat through the oxidative stress; (2) the consequence of B1R activation on stereotypic nocifensive behavior; (3) the role of downstream putative mediators in B1R-induced behavioral activity. Sprague-Dawley rats were fed with 10% D-glucose in their drinking water or tap water (controls) for 4 or 12 weeks, combined either with a standard chow diet or a diet enriched with α-lipoic acid (1 g/kg feed) for 4 weeks. The distribution and density of brain B1R binding sites were assessed by autoradiography. Behavioral activity evoked by i.c.v. injection of the B1R agonist Sar-[D-Phe(8)]-des-Arg(9)-BK (10 μg) was measured before and after i.c.v. treatments with selective antagonists (10 μg) for kinin B1 (R-715, SSR240612), tachykinin NK1 (RP-67580) and glutamate NMDA (DL-AP5) receptors or with the inhibitor of NOS (L-NNA). Results showed significant increases of B1R binding sites in various brain areas of glucose-fed rats that could be prevented by the diet containing α-lipoic acid. The B1R agonist elicited head scratching, grooming, sniffing, rearing, digging, licking, face washing, wet dog shake, teeth chattering and biting in glucose-fed rats, which were absent after treatment with α-lipoic acid or antagonists/inhibitors. Data suggest that kinin B1R is upregulated by the oxidative stress in the brain of insulin-resistant rats and its activation causes stereotypic nocifensive behavior through the release of substance P, glutamate and NO.
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Jenny Pena
authors.initials: JP
authors.lastname: Dias
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Helaine De Brito
authors.initials: Hde B
authors.lastname: Gariépy
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Brice
authors.initials: B
authors.lastname: Ongali
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada. Electronic address: rejean.couture@umontreal.ca.
authors.forename: Réjean
authors.initials: R
authors.lastname: Couture
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004149:Dioxoles / Q000008:administration & dosage; D018698:Glutamic Acid / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D043783:Receptor, Bradykinin B1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000502:physiology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: C487113:2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide; D004149:Dioxoles; D007328:Insulin; D043783:Receptor, Bradykinin B1; D013449:Sulfonamides; D009569:Nitric Oxide; D013373:Substance P; D018698:Glutamic Acid
keywords: Alpha-lipoic acid; Glutamate; Kinin B1 receptor; Nitric oxide; Substance P; Tachykinin NK1 receptor