Laboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan; Department of Orthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
Laboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
Brain Res. 2019 Jul 15;1715:115-125. doi: 10.1016/j.brainres.2019.03.015. Epub 2019 Mar 18.
Prostaglandin E (PGE) synthesized in the central nervous system influences various physiological functions including nociception. Recently, we have demonstrated that PGE facilitates spontaneous synaptic transmission through presynaptic EP1 receptors in the spinal trigeminal subnucleus caudalis (Vc) neurons that receive nociceptive signals from the orofacial area. Increasing evidence suggests that the action of PGE is related to activation of transient receptor potential vanilloid 1 (TRPV1) channels. The present study investigated whether TRPV1 channels contribute to the facilitatory effect of PGE on synaptic transmission in the Vc neurons. Spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) were recorded from Vc neurons in the rat brainstem slice by whole-cell patch-clamp mode. Superfusion of capsaicin (0.3, 1.0 μM) concentration-dependently increased the frequency of both sEPSCs and sIPSCs without any significant effect on their amplitude. The effect of capsaicin was completely abolished by a TRPV1 channel blocker AMG9810 (0.1 μM). PGE (5.0 μM) increased the frequency of sEPSCs and sIPSCs. This facilitatory effect of PGE was attenuated by AMG9810 and in neurons desensitized by repeated application of capsaicin. While a low concentration of either PGE (1.0 μM) or capsaicin (0.1 μM) had an insignificant effect on the sEPSCs and sIPSCs, co-application of these drugs increased their frequency. The present study demonstrated involvement of the presynaptic TRPV1 channels in PGE-induced facilitation of spontaneous synaptic transmissions and suggests interaction of PGE with TRPV1 channels in modification of nociceptive signals from the orofacial area to the Vc neurons.
前列腺素 E（PGE）在中枢神经系统中合成，影响各种生理功能，包括伤害感受。最近，我们已经证明，PGE 通过脊髓三叉神经亚核尾端（Vc）神经元中的突触前 EP1 受体促进自发性突触传递，这些神经元接收来自口腔面部区域的伤害感受信号。越来越多的证据表明，PGE 的作用与瞬时受体电位香草酸 1（TRPV1）通道的激活有关。本研究探讨了 TRPV1 通道是否有助于 PGE 对 Vc 神经元突触传递的促进作用。通过全细胞膜片钳模式，从大鼠脑干切片中的 Vc 神经元记录自发性兴奋性和抑制性突触后电流（sEPSC 和 sIPSC）。辣椒素（0.3、1.0μM）浓度依赖性地增加 sEPSC 和 sIPSC 的频率，而对其幅度没有任何显著影响。辣椒素的作用被 TRPV1 通道阻断剂 AMG9810（0.1μM）完全阻断。PGE（5.0μM）增加 sEPSC 和 sIPSC 的频率。这种 PGE 的促进作用被 AMG9810 减弱，并且在重复应用辣椒素使神经元脱敏的情况下减弱。虽然 PGE（1.0μM）或辣椒素（0.1μM）的低浓度对 sEPSC 和 sIPSC 没有显著影响，但这些药物的共同应用增加了它们的频率。本研究表明，突触前 TRPV1 通道参与了 PGE 诱导的自发性突触传递的促进作用，并表明 PGE 与 TRPV1 通道在修饰来自口腔面部区域到 Vc 神经元的伤害感受信号方面的相互作用。
