Abstract
Abstract The purpose of this study was to explore the inhibitory effect of α-methyl-5- hydroxytryptamine (α-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 α-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 α-methyl-5-HT. The dose-response curve for IATP showed that α-methyl-5-HT significantly shifted it. The Kd values of ATP-activated currents before and after the pre-addition of α-methyl-5-HT were similar (4.23×10-5 mol/L vs. 6.81×10-5 mol/L). Furthermore, cyproheptadine (10-6 mol/L), an antagonist of 5-HT2 receptor, can reverse the inhibition of α-methyl-5-HT. After intracellular dialysis of KN93 (CaMKII inhibitor) and H7 (PKC inhibitor), this inhibition was also completely eliminated. In conclusion, our results showed that α-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.
Highlights
The spinal dorsal horn is the primary center of sensory information integration
It is the primary gateway of peripheral nociceptive information transmission, and the the termination site of the descending system which originates from the brainstem and inhibits the noxious information transmission
It was reported that ATP transmitters released by dorsal root ganglion (DRG) neurons and membrane ATP receptors mediated responses were related to the transmission and modulation of pain information (Hu et al, 2017; Lü et al, 2017)
Summary
The spinal dorsal horn is the primary center of sensory information integration. It is the primary gateway of peripheral nociceptive information transmission, and the the termination site of the descending system which originates from the brainstem and inhibits the noxious information transmission. Thereafter, the pharmacological properties of ATP receptors in DRG cell membrane (Bean, 1990), the kinetics of receptor activation (Krishtal et al, 1988), the ionic mechanism of ATPactivated current (Li et al, 1993) and its modulation (Hu & Li, 1996) were studied in depth. We have done a series of work on the interaction between ATP receptors and other receptors in DRG cells (Wang et al, 2001; Skagerberg & Lindvall, 1985)
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