首页> 外文期刊>American Journal of Physiology >Regulatory pathways and uptake of L-DOPA by capillary cerebral endothelial cells, astrocytes, and neuronal cells.
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Regulatory pathways and uptake of L-DOPA by capillary cerebral endothelial cells, astrocytes, and neuronal cells.

机译:毛细血管内皮细胞,星形胶质细胞和神经元细胞对L-DOPA的调节途径和摄取。

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We examined the nature and regulation of the inward L-3,4-dihydroxyphenylalanine (L-DOPA) transporter in rat capillary cerebral endothelial (RBE4) cells, type 1 astrocytes (DI TNC1), and Neuro-2a neuroblastoma cells. In all three cell types, the inward transfer of L-DOPA was largely promoted through the 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid-sensitive and sodium-independent L-type amino acid transporter. Only in DI TNC1 cells was the effect of maneuvers that increase intracellular cAMP levels accompanied by increases in L-DOPA uptake. Also, only in DI TNC1 cells was the effect of the guanylyl cyclase inhibitor LY-83583 accompanied by a 65% increase in L-DOPA accumulation, whereas the nitric oxide donor sodium nitroprusside produced a 25% decrease in L-DOPA accumulation. In all three cell types, the Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L-DOPA uptake in a noncompetitive manner. Thapsigargin (1 and 3 microM) and A-23187 (1 and 3 microM) failed to alter L-DOPA accumulation in RBE4 and Neuro-2a cells but markedly increased L-DOPA uptake in DI TNC1 cells. We concluded that L-DOPA in RBE4, DI TNC1, and Neuro-2a cells is transported through the L-type amino acid transporter and appears to be under the control of Ca2+/calmodulin-mediated pathways. Astrocytes, however, are endowed with other processes that appear to regulate the accumulation of L-DOPA, responding positively to increases in intracellular Ca2+ and cAMP and to decreases in cGMP.
机译:我们检查了大鼠毛细血管内皮细胞(RBE4),1型星形胶质细胞(DI TNC1)和Neuro-2a神经母细胞瘤细胞中向内L-3,4-二羟基苯丙氨酸(L-DOPA)转运蛋白的性质和调控。在所有这三种细胞类型中,L-DOPA的向内转移很大程度上是通过2-氨基双环-(2,2,1)-庚烷-2-羧酸敏感性和钠依赖性L型氨基酸转运蛋白来促进的。仅在DI TNC1细胞中,操纵的作用增加了细胞内cAMP水平,并伴随着L​​-DOPA摄取的增加。同样,仅在DI TNC1细胞中,鸟苷酰环化酶抑制剂LY-83583的作用伴随着L-DOPA积累增加65%,而一氧化氮供体硝普钠减少了L-DOPA积累25%。在所有三种细胞类型中,Ca2 + /钙调蛋白抑制剂Calidazolium和trifluoperazine以非竞争性方式抑制L-DOPA摄取。 Thapsigargin(1和3 microM)和A-23187(1和3 microM)未能改变RBE4和Neuro-2a细胞中L-DOPA的积累,但显着增加了DI TNC1细胞中L-DOPA的摄取。我们得出的结论是,RBE4,DI TNC1和Neuro-2a细胞中的L-DOPA通过L型氨基酸转运蛋白转运,并且似乎受Ca2 + /钙调蛋白介导的途径的控制。然而,星形胶质细胞具有其他过程,这些过程似乎可以调节L-DOPA的积累,对细胞内Ca2 +和cAMP的增加以及cGMP的减少有积极的反应。

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