Potentiation of ASIC currents by lysophosphatidic acid in rat dorsal root ganglion neurons

Lysophosphatidic acid (LPA) is a phospholipid which has been implicated in pain. Acid-sensing ion channels (ASICs) are important players in pain associated with tissue acidification. However, it is still unclear whether there is a link between LPA signaling and ASICs in pain processes. Herein, we show that a functional interaction between them in rat dorsal root ganglia (DRG) neurons. Pre-application of LPA enhanced ASIC-mediated and acid-evoked inward currents in a concentration-dependent manner. LPA shifted the concentration-response curve for protons upwards, with an increase of 41.79 ± 4.71% in the maximal current response of ASICs to protons in the presence of LPA. Potentiation of ASIC currents by LPA was blocked by the LPA1 receptor antagonist Ki16198, but not by the LPA2 receptor antagonist H2L5185303. The LPA-induced potentiation was also prevented by intracellular application of either G protein inhibitor or protein kinase C (PKC) inhibitor, but not by Rho inhibitor. LPA also enhanced ASIC3 currents in CHO cells co-expressing ASIC3 and LPA1 receptors, but not in cells expressing ASIC3 alone. Moreover, LPA increased the amplitude of the depolarization and the number of spikes induced by acid stimuli. Finally, LPA exacerbated acid-induced nociceptive behaviors in rats. These results suggested that LPA enhanced ASIC-mediated electrophysiological activity and nociception via a LPA1 receptor and its downstream PKC rather than Rho signaling pathway, which provided a novel peripheral mechanism underlying the sensitization of pain.

 

Comments：

The passage describes a study that investigated the relationship between lysophosphatidic acid (LPA) and acid-sensing ion channels (ASICs) in pain processes. The study found that LPA enhances ASIC-mediated and acid-evoked inward currents in rat dorsal root ganglia (DRG) neurons, and potentiates ASIC3 currents in cells co-expressing ASIC3 and LPA1 receptors. The potentiation of ASIC currents by LPA is mediated through the LPA1 receptor and downstream protein kinase C (PKC) signaling pathway, rather than the Rho signaling pathway. LPA also increases the amplitude of depolarization and the number of spikes induced by acid stimuli, and exacerbates acid-induced nociceptive behaviors in rats. These findings suggest that LPA may play a role in sensitizing pain through its interaction with ASICs in the peripheral nervous system.

Related Products

Cat.No.	Product Name	Information
S2906	Ki16198	Ki16198 is the methyl ester of Ki16425, which is a LPA antagonist and inhibits LPA1- and LPA3-induced inositol phosphate production with Ki of 0.34 μM and 0.93 μM, respectively, shows weaker inhibition for LPA2, no activity at LPA4, LPA5, LPA6.

Related Targets

LPA Receptor