The Modulation Of Capsaicin Receptor By Cannabinoids In Rat Trigeminal Ganglion Neurons

Although the inhibitory effect of cannabinoids on 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 anandamide (AEA, an endogenous cannabinoid) and WIN55,212-2 (WIN, a synthetic cannabinoid) inhibited TRPV1 in rat trigeminal ganglion neurons. The concentration dependence of the effect of AEA and WIN on Icap was studied:a "bell" shaped concentration dependent curve was obtained with very low threshold (less than 10-15 M for both AEA and WIN). The maximal inhibitions were at concentration 10-10M and 10-9M, and at these concentrations the Icap was reduced by 89±7.5% and 95±1.6% respectively. When the concentration of AEA or WIN was higher than 10-5M, inhibitory effects were completely reversed. In this study several intracellular signaling transduction pathways were tested to study whether they were involved in the inhibitory effects of AEA or WIN on capsaicin-induced current (Icap).It was newly 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-βs and PLC antagonist U73122 had no effect on the inhibitory effect. It suggests that several intracellular signaling transduction pathways underlie the inhibitory effects of cannabinoids on Icap,including PKA and PKC systems. This experiment aimed to investigate the modulation of osmolality on 5-HT-activated currents(I5-HT) in primary sensory neurons. Whole cell-patch clamp recording was performed on cultured SD rat trigeminal ganglion (TG) neurons. (1) The majority of examined neurons (75%) were sensitive to 5-HT (3-300μM).5-HT3 receptor activated inward currents in a concentration-dependent manner, and I5-HT3 were blocked by ICS 205-930 (1μM), a selective antagonist of the 5-HT3 receptor. (2) 100μM 5-HT was repeated exerted for every three minut, and 5-HT3 receptor activated inward currents had no change. (3) When 260mOsm was preapplied extracellularly,5-HT3 receptor activated inward currents had no change. (4) When 348mOsm was preapplied extracellularly,5-HT3 receptor activated inward currents also had no change. It suggests that osmolality has no modulation on 5-HT3 receptor activated current.