Rusin K I, Bleakman D, Chard P S, Randic M, Miller R J
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames.
J Neurochem. 1993 Mar;60(3):952-60. doi: 10.1111/j.1471-4159.1993.tb03242.x.
Substance P and neurokinin A both potentiated N-methyl-D-aspartate (NMDA)-induced currents recorded in acutely isolated neurons from the dorsal horn of the rat. To elucidate the mechanism underlying this phenomenon, we measured the effects of tachykinins and glutamate receptor agonists on [Ca2+]i in these cells. Substance P, but not neurokinin A, increased [Ca2+]i in a subpopulation of neurons. The increase in [Ca2+]i was found to be due to Ca2+ influx through voltage-sensitive Ca2+ channels. Substance P and neurokinin A also potentiated the increase in [Ca2+]i produced by NMDA, but not by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, or 50 mM K+. Phorbol esters enhanced the effects of NMDA and staurosporine inhibited the potentiation of NMDA effects by tachykinins. It is concluded that activation of protein kinase C may mediate the enhancement of NMDA effects by tachykinins in these cells. However, the effects of tachykinins on [Ca2+]i can be dissociated from their effects on NMDA receptors.
P物质和神经激肽A均可增强在急性分离的大鼠背角神经元中记录到的N-甲基-D-天冬氨酸（NMDA）诱导的电流。为了阐明这一现象背后的机制，我们测量了速激肽和谷氨酸受体激动剂对这些细胞内钙离子浓度（[Ca2+]i）的影响。P物质而非神经激肽A可使一部分神经元的[Ca2+]i升高。发现[Ca2+]i的升高是由于钙离子通过电压敏感性钙通道内流所致。P物质和神经激肽A还可增强NMDA所引起的[Ca2+]i升高，但对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸、海人藻酸或50 mM钾离子所引起的[Ca2+]i升高无增强作用。佛波酯可增强NMDA的作用，而星形孢菌素可抑制速激肽对NMDA作用的增强。得出的结论是，蛋白激酶C的激活可能介导了速激肽在这些细胞中对NMDA作用的增强。然而，速激肽对[Ca2+]i的作用可与其对NMDA受体的作用相分离。
