title: Brain kinin B₁ receptor contributes to the onset of stereotypic nocifensive behavior in rat.
abstract: While brain kinin B(1) receptor (B(1)R) is virtually absent in control rats, it contributes to hypertension via a midbrain dopaminergic (DA) mechanism in spontaneously hypertensive rat (SHR) and Angiotensin II (Ang II)-induced hypertension. This study aims at determining whether B(1)R can also affect stereotypic nocifensive behavior through DA and/or other neuromediators in the same models. The selective B(1)R agonist Sar[D-Phe(8)][des-Arg(9)]BK was injected i.c.v. (1 μg/site) to freely behaving SHR (16 weeks), Ang II-hypertensive rats (200 ng/kg/min × 2 weeks, s.c.) and control Wistar-Kyoto rats (WKY). Behavioral activity to the agonist was measured before and after treatment with receptor antagonists (10 μg/site i.c.v. or otherwise stated) for B(1) (SSR240612), tachykinin NK(1) (RP67580), glutamate NMDA (DL-AP5), DA D(1) (SCH23390, 0.2mg/kg s.c.) and D(2) (Raclopride, 0.16 mg/kg s.c.). Other studies included inhibitors (10 μg/site) of NOS (l-NNA) and iNOS (1400W). The possible desensitisation of B(1)R upon repeated intracerebral stimulation was also excluded. B(1)R expression was measured by qRT-PCR in selected areas and by immunohistochemistry in the ventral tegmental area. Results showed that the B(1)R agonist had no effect in WKY, yet it induced nocifensive behavioral manifestations in both models of hypertension (face washing, sniffing, head scratching, rearing, teeth chattering, grooming, digging, licking, wet-dog shakes). These responses were prevented by all antagonists and inhibitors tested, but 1400 W had a less inhibitory effect on most behaviors. Compared with WKY, B(1)R mRNA levels were markedly enhanced in hypothalamus, ventral tegmental area and nucleus accumbens of SHR and Ang II-treated rats. B(1)R was detected on DA neuron of the ventral tegmental area in SHR. Data suggest that kinin B(1)R is upregulated in midbrain DA system in hypertensive rats and its i.c.v. activation induced stereotypic nocifensive behavior that is mediated by several mediators, notably substance P, glutamate, DA and NO.
authors.affiliation: Department of Physiology, Faculty of Medicine, Université de Montréal, CP 6128, Succursale Centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: H
authors.initials: H
authors.lastname: De Brito Gariepy
authors.forename: S
authors.initials: S
authors.lastname: Talbot
authors.forename: J
authors.initials: J
authors.lastname: Sénécal
authors.forename: R
authors.initials: R
authors.lastname: Couture
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D065169:Bradykinin B1 Receptor Antagonists; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D054833:Isoindoles / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D043783:Receptor, Bradykinin B1 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects*; D013373:Substance P / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology
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; D001552:Benzazepines; D065169:Bradykinin B1 Receptor Antagonists; D004149:Dioxoles; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D054833:Isoindoles; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; C534628:SCH 23390; D013449:Sulfonamides; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D020891:Raclopride; D015763:2-Amino-5-phosphonovalerate