Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity.
The capsaicin receptor transient receptor potential V1 (TRPV1; also known as vanilloid receptor 1) is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. It has been reported that extracellular ATP potentiates the TRPV1 currents evoked by capsaicin or protons and reduces the temperature threshold for its activation through metabotropic P2Y receptors in a PKC-dependent pathway, suggesting that TRPV1 activation could trigger the sensation of pain at normal body temperature in the presence of ATP. Here, we show that ATP-induced thermal hyperalgesia was abolished in mice lacking TRPV1, suggesting the functional interaction between ATP and TRPV1 at a behavioral level. However, thermal hyperalgesia was preserved in P2Y1 receptor-deficient mice. Patch-clamp analyses using mouse dorsal root ganglion neurons indicated the involvement of P2Y2 rather than P2Y1 receptors. Coexpression of TRPV1 mRNA with P2Y2 mRNA, but not P2Y1 mRNA, was determined in the rat lumbar DRG using in situ hybridization histochemistry. These data indicate the importance of metabotropic P2Y2 receptors in nociception through TRPV1.
Moriyama
Tomoko
T
Department of Cellular and Molecular Physiology, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
Iida
Tohko
T
Kobayashi
Kimiko
K
Higashi
Tomohiro
T
Fukuoka
Tetsuo
T
Tsumura
Hideki
H
Leon
Catherine
C
Suzuki
Noboru
N
Inoue
Kazuhide
K
Gachet
Christian
C
Noguchi
Koichi
K
Tominaga
Makoto
M
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects; D006987:Hypesthesia / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010147:Pain Measurement; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011955:Receptors, Drug / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D050916:TRPV Cation Channels; D014544:Uridine Triphosphate / Q000494:pharmacology
C546383:P2ry1 protein, mouse; C546384:P2ry1 protein, rat; C546386:P2ry2 protein, mouse; C546387:P2ry2 protein, rat; D012333:RNA, Messenger; D011955:Receptors, Drug; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D000255:Adenosine Triphosphate; D002211:Capsaicin; D014544:Uridine Triphosphate