Acute PAR2 activation reduces alpha, beta-MeATP sensitive currents in rat dorsal root ganglion neurons.
It has been reported that proteinase-activated receptor 2 (PAR2) receptor activation enhances the animal's pain response and PAR2 coexpresses with P2X3 in dorsal root ganglion neurons. However, whether PAR2 activation has a direct impact on P2X3 currents is still not clear. In this study, we performed the patch-clamp experiments in cultured dorsal root ganglion neurons and found that when incubated with trypsin or the PAR2 agonist SL-NH2 for a short time (3 min), instead of increasing, P2X3 currents amplitude decreased significantly. Meanwhile, the opening of P2X3 ion channel accelerated. Protein kinase A inhibitor H89 could not reverse above phenomenon, but played a synergistic effect on the contrary. These results suggest that the enhanced pain response caused by PAR2 activation is not through direct increase of the P2X3 current amplitude, and the acceleration of P2X3 opening may participate in the enhanced pain response in a long-time view. Moreover, protein kinase A does not participate in the inhibition of P2X3 currents caused by PAR2 activation.
Lu
Zhi-Jie
ZJ
Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
Miao
Xue-Rong
XR
Wu
Jing-Xiang
JX
Wang
Xiao-Yan
XY
Miao
Qing
Q
Yu
Wei-Feng
WF
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D044464:Receptor, PAR-2 / Q000187:drug effects / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3; D014357:Trypsin / Q000494:pharmacology
C546410:P2rx3 protein, rat; D044464:Receptor, PAR-2; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate; D014357:Trypsin