Evans A R, Nicol G D, Vasko M R
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, USA.
Brain Res. 1996 Mar 18;712(2):265-73. doi: 10.1016/0006-8993(95)01447-0.
To determine whether the sensitizing action of prostaglandins on sensory neurons are due to modulation of voltage-sensitive calcium channels (VSCC) we examined the effects of inhibiting these channels on PGE2-induced enhancement of evoked peptide release from isolated dorsal root ganglion neurons. The inhibitory effects of the VSCC blockers on stimulated release were dependent upon the type of chemical agent used to evoke the release. Bradykinin-stimulated release of immunoreactive substance P (iSP) and calcitonin gene-related peptide (iCGRP) was attenuated by the N-type VSCC blocker, omega-conotoxin GVIA (100 nM), but was unaffected by blockade of L-type (1 microM nifedipine) or P-type (200 nM omega-agatoxin IVA) VSCC. In contrast, potassium-stimulated release of peptides was inhibited by nifedipine, but not by omega-conotoxin GVIA or omega-agatoxin IVA. None of the VSCC blockers tested attenuated capsaicin-stimulated release of iSP and iCGRP. The combination of 1 microM nifedipine and 100 nM omega-conotoxin GVIA reduced the whole cell calcium current 89% +/- 1.7%. Administration of 100 nM PGE2 potentiated bradykinin- and capsaicin-evoked peptide release by 2-3-fold. Neither nifedipine nor omega-conotoxin GVIA attenuated the PGE2-mediated potentiation of bradykinin-evoked release, and neither omega-conotoxin GVIA nor omega-agatoxin IVA blocked the potentiation of capsaicin-evoked release induced by PGE2. These results indicate that the sensitizing actions of PGE2 as measured by enhanced peptide release, are not mediated by L-, N-, or P-type VSCC.
为了确定前列腺素对感觉神经元的致敏作用是否归因于电压敏感性钙通道（VSCC）的调节，我们研究了抑制这些通道对前列腺素E2（PGE2）诱导的离体背根神经节神经元诱发肽释放增强的影响。VSCC阻滞剂对刺激释放的抑制作用取决于用于诱发释放的化学试剂类型。N型VSCC阻滞剂ω-芋螺毒素GVIA（100 nM）减弱了缓激肽刺激的免疫反应性P物质（iSP）和降钙素基因相关肽（iCGRP）的释放，但L型（1 μM硝苯地平）或P型（200 nM ω-阿加毒素IVA）VSCC的阻断对其没有影响。相反，硝苯地平抑制了钾刺激的肽释放，但ω-芋螺毒素GVIA或ω-阿加毒素IVA没有。所测试的VSCC阻滞剂均未减弱辣椒素刺激的iSP和iCGRP释放。1 μM硝苯地平和100 nM ω-芋螺毒素GVIA的组合使全细胞钙电流降低了89%±1.7%。给予100 nM PGE2可使缓激肽和辣椒素诱发的肽释放增强2至3倍。硝苯地平和ω-芋螺毒素GVIA均未减弱PGE₂介导的缓激肽诱发释放的增强作用，ω-芋螺毒素GVIA和ω-阿加毒素IVA均未阻断PGE₂诱导的辣椒素诱发释放的增强作用。这些结果表明，通过增强肽释放所测量的PGE₂的致敏作用不是由L型、N型或P型VSCC介导的。
