Inhibition of P2X receptor-mediated inward current by protein kinase C in small-diameter dorsal root ganglion neurons of adult rats.

OBJECTIVE: The aim of the present study is to verify the ATP-induced varied responses in isolated dorsal root ganglion (DRG) neurons of the adult rat, and investigate the modulatory effects of specific P2X receptor agonist beta, gamma-me-ATP and protein kinase C (PKC) on P2X receptor-mediated inward current in DRG neurons. METHODS: Whole cell patch-clamp was employed to record the currents on acutely isolated DRG neurons in the adult rats. RESULTS: beta, gamma-me-ATP, similar as ATP, evoked 2 distinct subtypes of P2X receptor-mediated inward currents in a dose-dependent manner in DRG neurons. Activation of PKC by phorbol 12, 13-dibutyrate (PDBu) significantly inhibited both subtypes of inward currents mediated by P2X receptors in a dose-dependent manner. CONCLUSION: Activation of PKC negatively modulated the P2X receptor-mediated currents in rat DRG neurons, which may be of benefit to preventing the over-excitation of nociceptor under inflammatory or neuropathic conditions.

Ligustrazine inhibits high voltage-gated Ca(2+) and TTX-resistant Na(+) channels of primary sensory neuron and thermal nociception in the rat: a study on peripheral mechanism.

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinociceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency (PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25 mu l) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC(50) of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC(50) of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.