title: Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1.
abstract: Bradykinin (BK) is an inflammatory mediator that plays a pivotal role in pain and hyperalgesia to heat in inflamed tissues by exciting nociceptors and sensitizing them to heat through activation of protein kinase C (PKC). It has been suggested that the capsaicin receptor (VR1), a nociceptor-specific cation channel sensitive to noxious heat, protons, and capsaicin, is a channel that is modified by BK in these effects. In this study, we examined how BK modulates the activity of VR1. We measured VR1 currents using the patch-clamp technique in human embryonic kidney-derived (HEK293) cells expressing VR1 and B2 BK receptor. We found that BK lowered the threshold temperature for activation of VR1 currents in HEK cells down to well below the physiological body temperature in a concentration-dependent manner through PKC activation. We also demonstrated that in capsaicin-sensitive dorsal root ganglion (DRG) neurons the activation threshold of heat-induced current, which is considered to be VR-1 mediated, was lowered by BK and that this effect was also mediated by PKC. These data further support the supposition that modulation of VR1 is a mechanism for the BK-induced excitation of nociceptors and their sensitization to heat.
authors.affiliation: Department of Anesthesiology and Resuscitology, Nagoya City University Medical School, Nagoya 467-0001, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugiura
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
authors.forename: Hirotada
authors.initials: H
authors.lastname: Katsuya
authors.forename: Kazue
authors.initials: K
authors.lastname: Mizumura
mesh_terms: D001920:Bradykinin / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D002460:Cell Line; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D006358:Hot Temperature; D006801:Humans; D011955:Receptors, Drug / Q000502:physiology*; D012684:Sensory Thresholds / Q000187:drug effects*
chemical_list: D011955:Receptors, Drug; D002211:Capsaicin; D001920:Bradykinin