The inhibitory effect of α-methyl-5-HT on ATP-activated currents in rat dorsal root ganglion neurons

The purpose of this study was to explore the inhibitory effect of alpha-methyl-5- hydroxytryptamine (alpha-methyl-5-HT) on ATP-activated current (IATP) in rat dorsal root ganglion (DRG) neurons. Whole-cell patch clamp experiment was performed on cultured rat DRG neurons. One minute after treatment with alpha-methyl-5-HT, ATP (10(-4) mol/L) activation current in rat DRG neurons was inhibited. However, this inhibitory effect was independent of the current caused by alpha-methyl-5-HT. The dose-response curve for IATP showed that alpha-methyl-5-HT significantly shifted it. The Kd values of ATP-activated currents before and after the pre-addition of alpha-methyl-5-HT were similar (4.23x10(-5) mol/L vs. 6.81x10(-5) mol/L). Furthermore, cyproheptadine (10(-6) mol/L), an antagonist of 5-HT2 receptor, can reverse the inhibition of alpha-methyl-5-HT. After intracellular dialysis of KN93 (CaMKII inhibitor) and 117 (PKC inhibitor), this inhibition was also completely eliminated. In conclusion, our results showed that alpha-methyl-5-HT inhibited ATP-activated current through activating the 5-HT2 receptor and resulting in phosphorylation of the ATP receptor. It was caused by the activation of G protein coupled receptor and corresponding intracellular signaling transduction cascade.