[Pain and Bradykinin Receptors--sensory transduction mechanism in the nociceptor terminals and expression change of bradykinin receptors in inflamed condition].
Nihon Shinkei Seishin Yakurigaku Zasshi
; 25(1): 33-8, 2005 Feb.
Article
en Ja
| MEDLINE
| ID: mdl-15796068
ABSTRACT
Bradykinin (BK), an endogenous algesic and sensitizing substance, excited nociceptors and sensitized their heat responses. These effects were mediated by B2 receptors (B2Rs) in normal condition, and B1 receptors were additionally recruited in inflammation. B2Rs were coupled with Gq/11 and their activation resulted in diacylglycerol and inositol triphosphate release. Diacylglycerol activated protein kinase (PK) Cepsilon in sensory neurons. To clarify what channel was modulated by PKC to depolarize nociceptor terminals, we examined the heat activation threshold (Tt) of heat-sensitive capsaicin receptor (TRPV1). Tt was lowered down to 31 degrees C by BK in concentration dependent manner through activation of PKCepsilon in cells heterologously expressing TRPV1 and B2Rs. Thus both excitation and sensitization to heat could be explained by one mechanism, lowering Tt of TRPV1. The same was observed in capsaicin-sensitive primary sensory neurons. However, TRPV1 knockout mice showed almost no change in BK-induced nociceptive behavior and nociceptor excitation, although BK-induced heat hyperalgesia completely disappeared, suggesting that TRPV1 was not the sole channel that was modulated by BK to depolarize nociceptor terminals. In addition nociceptor sensitivity to BK was augmented in inflamed animals, with B2R mRNA and protein upregulated. The mechanism for prostaglandin-induced augmentation of BK response is left open for future study.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nociceptores
/
Receptores de Bradiquinina
/
Mecanotransducción Celular
Límite:
Animals
Idioma:
Ja
Revista:
Nihon Shinkei Seishin Yakurigaku Zasshi
Asunto de la revista:
PSICOFARMACOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Japón