Hillard C J
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Neuropharmacology. 1992 Sep;31(9):909-14. doi: 10.1016/0028-3908(92)90129-d.
Earlier studies from this laboratory demonstrated that activation of nicotinic cholinergic receptors of cerebral cortical synaptosomes of the rat produced a decrease in the accumulation of [3H]tetraphenylphosphonium ([3H]TPP+) as a result of a decreased synaptosomal membrane potential. In the present study, the role of sodium in the effect of nicotine on the accumulation of [3H]TPP+ and the estimated potential difference was explored. Replacement of buffer sodium with either sucrose or N-methyl-D-glucamine (NMDG), attenuated the depolarization produced by the sodium channel activator, veratridine and had no effect on potassium-induced depolarization. The effect of nicotine on accumulation of [3H]TPP+ into cerebral cortical synaptosomes was abolished in sucrose buffer and attenuated in NMDG buffer. 1,1-Dimethyl-4-phenylpiperazinium iodide (DMP; 30 microM) produced a small increase in the influx of 22Na+ into cerebral cortical synaptosomes. The effect of DMPP on the influx of 22 Na+ was not blocked by tetrodotoxin. These results support the hypothesis that the nicotinic cholinergic receptor in the brain, functions as a sodium ionophore and further demonstrate that accumulation of synaptosomal [3H]TPP+ provides a simple tool with which to assess the effect of nicotine on sodium permeability through open nicotinic cholinergic receptor ionophores.
该实验室早期的研究表明，大鼠大脑皮质突触体烟碱型胆碱能受体的激活会导致[3H]四苯基鏻（[3H]TPP+）积累减少，这是突触体膜电位降低的结果。在本研究中，探讨了钠在尼古丁对[3H]TPP+积累及估计电位差影响中的作用。用蔗糖或N-甲基-D-葡糖胺（NMDG）替代缓冲液中的钠，可减弱钠通道激活剂藜芦定引起的去极化，且对钾诱导的去极化无影响。在蔗糖缓冲液中，尼古丁对大脑皮质突触体中[3H]TPP+积累的影响消失，在NMDG缓冲液中则减弱。1,1-二甲基-4-苯基哌嗪碘化物（DMP；30微摩尔）使22Na+流入大脑皮质突触体略有增加。DMPP对22Na+流入的影响未被河豚毒素阻断。这些结果支持以下假设：大脑中的烟碱型胆碱能受体作为钠离子载体发挥作用，并进一步证明突触体[3H]TPP+的积累提供了一种简单工具，可用于评估尼古丁对通过开放的烟碱型胆碱能受体离子载体的钠通透性的影响。
