[Pain and Bradykinin Receptors--sensory transduction mechanism in the nociceptor terminals and expression change of bradykinin receptors in inflamed condition].
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.
Mizumura
Kazue
K
Department of Neural Regulation, Research Institute of Environmental Medicine, Nagoya University, Nagoya, 464-8601, Japan. mizu@riem.nagoya-u.ac.jp
Sugiur
Takeshi
T
Koda
Hisashi
H
Katanosaka
Kimiaki
K
Kumar
Banik Ratan
BR
Giron
Rocio
R
Tominaga
Makoto
M
D000818:Animals; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D009619:Nociceptors / Q000502:physiology*; D018002:Receptors, Bradykinin / Q000502:physiology*
D018002:Receptors, Bradykinin