[Molecular mechanisms of nociception].
Capsaicin, the main ingredient in 'hot' chili peppers, elicits burning pain by activating nociceptors. The cloned capsaicin receptor (TRPV1) is a nonselective cation channel with six transmembrane domains, and is activated not only by capsaicin but also by noxious heat (> 43 degrees C) or protons (acidification), both of which cause pain in vivo. Furthermore, analyses of mice lacking VR1 showed that VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia. Tissue damage produces an array of chemical mediators that activate or sensitize nociceptor terminals to elicit pain. Important components of this pro-algesic response are ATP and bradykinin. In cells expressing TRPV1, ATP or bradykinin increased the currents evoked by capsaicin or protons through activation of metabotropic P2Y or B2 bradykinin receptors. In the presence of ATP or bradykinin, the temperature threshold for VR1 activation was reduced from 42 degrees C to 30-35 degrees C, such that normally non-painful normal body temperatures were capable of activating TRPV1, thereby leading to the sensation of pain. Direct phosphorylation of TRPV1 by PKC epsilon was confirmed and the involved two serine residues were determined. This represents a novel mechanism through which ATP or bradykinin in response to tissue trauma might trigger the sensation of pain.
Tominaga
Makoto
M
Department of Cellular and Molecular Physiology, Mie University School of Medicine, 2-174, Edobashi, Tsu, 514-8507 Japan.
Numazaki
Mitsuko
M
Iida
Tohko
T
Tominaga
Tomoko
T
D062565:Acid Sensing Ion Channels; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001920:Bradykinin / Q000502:physiology; D006358:Hot Temperature; D007473:Ion Channels / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins; D009619:Nociceptors / Q000502:physiology*; D010146:Pain; D011522:Protons; D011955:Receptors, Drug / Q000235:genetics* / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology; D058469:Receptors, Purinergic P2X; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology; D050916:TRPV Cation Channels
C112231:ASIC3 protein, human; D062565:Acid Sensing Ion Channels; D007473:Ion Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011522:Protons; D011955:Receptors, Drug; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D015222:Sodium Channels; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D000255:Adenosine Triphosphate; D001920:Bradykinin