Cannabinoid WIN 55,212-2 inhibits TRPV1 in trigeminal ganglion neurons via PKA and PKC pathways
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Wei Wang • Xuehong Cao • Changjin Liu • Lieju Liu
- چاپ و سال / کشور: 2011
Description
Although the inhibitory effect of cannabinoids on transient receptor potential vanilloid 1 (TRPV1) channel may explain the efficacy of peripheral cannabinoids in antihyperalgesia and antinociceptive actions, the mechanism for cannabinoid-induced inhibition of TRPV1 in primary sensory neurons is not understood. Therefore, we explored how WIN55,212-2 (WIN, a synthetic cannabinoid) inhibited TRPV1 in rat trigeminal ganglion neurons. A ‘‘bell’’-shaped concentration-dependent curve was obtained from the effects of WIN on TRPV1 channel. The maximal inhibition on capsaicin-induced current (Icap) by WIN was at a concentration of 10-9 M, and at this concentration Icap was reduced by 95 ± 1.6%. When the concentration of WIN was at 10-6 M, it displayed a stimulatory effect on Icap. In this study, several intracellular signaling transduction pathways were tested to study whether they were involved in the inhibitory effects of WIN on Icap. We found that the inhibitory effect of WIN on Icap was completely reversed by PKA antagonists H-89 and KT5720 as well as by PKC antagonists BIM and staurosporine. It was also found that the inhibitory effect was partly reversed by PKG antagonist PKGi, while G-protein antagonist GDP-bs/pertussis toxin (PTX) and PLC antagonist U-73122 had no effect on the inhibitory effect of WIN on Icap. These results suggest that several intracellular signaling transduction pathways including PKA and PKC systems underlie the inhibitory effects of WIN on Icap; however, G protein-coupled receptors CB1 or CB2 were not involved.
Neurol Sci DOI 10.1007/s10072-011-0620-6, Received: 5 August 2010 / Accepted: 29 April 2011
