Nicol G D, Klingberg D K, Vasko M R
Department of Pharmacology and Toxicology, School of Medicine, Indiana University, Indianapolis 46202.
J Neurosci. 1992 May;12(5):1917-27. doi: 10.1523/JNEUROSCI.12-05-01917.1992.
Prostaglandins are known to lower activation threshold to thermal, mechanical, and chemical stimulation in small-diameter sensory neurons. Although the mechanism of prostaglandin action is unknown, agents known to elevate intracellular calcium produce a sensitization that is similar to that produced by prostaglandins. Consistent with the idea of prostaglandin-induced elevations in calcium, prostaglandins might also stimulate the release of neurotransmitter from sensory neurons. We therefore examined whether prostaglandin E2 (PGE2) could enhance the release of the putative sensory transmitter substance P (SP) from isolated neurons of the avian dorsal root ganglion grown in culture. Utilizing the whole-cell patch-clamp recording technique, we also examined whether PGE2 could alter calcium currents in these cells. Exposure of sensory neurons to PGE2 produced a dose-dependent increase in the release of SP. One micromolar PGE2 increased release approximately twofold above basal release, whereas 5 and 10 microM PGE2 increased release by about fourfold. The release evoked by these higher concentrations of PGE2 was similar in magnitude to the release induced by 50 mM KCl. Neither arachidonic acid (10 microM), prostaglandin F2 alpha (10 microM), nor the lipoxygenase product leukotriene B4 (1 microM) significantly altered SP release. The addition of 1 microM PGE2 increased the peak calcium currents by 1.8-fold and 1.4-fold for neurons held at potentials of -60 and -90 mV, respectively. The action of PGE2 was rapid with facilitation occurring within 2 min. As with release studies, arachidonic acid, prostaglandin F2 alpha, and leukotriene B4 had no significant effect on the amplitude of the calcium current. These results suggest that PGE2 can stimulate the release of SP through the activation or facilitation of an inward calcium current. The capacity of PGE2 to facilitate the calcium current in these sensory neurons may be one mechanism to account for the ability of prostaglandins to sensitize sensory neurons to physical or chemical stimuli.
已知前列腺素可降低小直径感觉神经元对热、机械和化学刺激的激活阈值。尽管前列腺素的作用机制尚不清楚，但已知能升高细胞内钙的药物会产生一种与前列腺素产生的致敏作用相似的致敏作用。与前列腺素诱导钙升高的观点一致，前列腺素也可能刺激感觉神经元释放神经递质。因此，我们研究了前列腺素E2（PGE2）是否能增强培养的鸡背根神经节分离神经元中假定的感觉递质P物质（SP）的释放。利用全细胞膜片钳记录技术，我们还研究了PGE2是否能改变这些细胞中的钙电流。将感觉神经元暴露于PGE2会导致SP释放呈剂量依赖性增加。1微摩尔PGE2使释放量比基础释放量增加约两倍，而5和10微摩尔PGE2使释放量增加约四倍。这些较高浓度的PGE2引起的释放量在幅度上与50毫摩尔氯化钾诱导的释放量相似。花生四烯酸（10微摩尔）、前列腺素F2α（10微摩尔）或脂氧合酶产物白三烯B4（1微摩尔）均未显著改变SP释放。添加1微摩尔PGE2分别使保持在-60和-90毫伏电位的神经元的峰值钙电流增加1.8倍和1.4倍。PGE2的作用迅速，在2分钟内就会出现促进作用。与释放研究一样，花生四烯酸、前列腺素F2α和白三烯B4对钙电流幅度没有显著影响。这些结果表明，PGE2可通过激活或促进内向钙电流来刺激SP释放。PGE2促进这些感觉神经元中钙电流的能力可能是解释前列腺素使感觉神经元对物理或化学刺激敏感的能力的一种机制。
