GUANINE NUCLEOTIDE-BINDING PROTEIN GO-INDUCED COUPLING OF NEUROPEPTIDE Y-RECEPTORS TO CA-2+ CHANNELS IN SENSORY NEURONS
GUANINE NUCLEOTIDE-BINDING PROTEIN GO-INDUCED COUPLING OF NEUROPEPTIDE Y-RECEPTORS TO CA-2+ CHANNELS IN SENSORY NEURONS
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DOI：
10.1073/pnas.85.10.3633
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发表时间：
1988-05-01
影响因子：
11.1
通讯作者：
MILLER, RJ
中科院分区：
文献类型：
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作者：
EWALD, DA;STERNWEIS, PC;MILLER, RJ
神经肽Y （NPY）体外抑制大鼠背根神经节神经元Ca2+电流（ICa）。NPY抑制了从-40 mV保持电位到0 mV所诱发的持续ICa和从-80 mV更负的保持电位所诱发的失活ICa。如果细胞首先用百日咳毒素（PTX）处理，则NPY对两相ICa的影响都被消除。当GTP和纯化的。将鸟嘌呤核苷酸结合蛋白Go的亚基灌注到ptx处理的细胞中，NPY对ICa的抑制作用以时间依赖性的方式重新出现。GTP或。alpha。-亚单位单独灌注相对无效。在较高浓度的。α。o下，NPY的作用重现得更快。用磷酯长期治疗这些细胞“下调”蛋白激酶C (PKC)，减少NPY对持续电流的抑制。在PKC被下调去除的ptx处理的细胞中，GTP/.alpha.o灌注后也重建了ICa的抑制。在这种情况下，NPY对瞬时ICa的抑制作用大于持续ICa的抑制作用。这些结果表明，中枢神经系统中主要的PTX底物Go可能在正常情况下介导NPY受体对背根神经节Ca2+通道的抑制作用。
Neuropeptide Y (NPY) inhibited the Ca2+ current (ICa) in rat dorsal root ganglion neurons in vitro. NPY inhibited the sustained ICa evoked by steps to 0 mV from a holding potential of -40 mV and the inactivating ICa, which was additionally evoked from a more negative holding potential of -80 mV. The effects of NPY on both phases of the ICa were abolished if cells were first treated with pertussis toxin (PTX). When a combination of GTP and the purified .alpha.-subunit of the guanine nucleotide-binding protein Go was perfused into PTX-treated cells, the inhibitory effects of NPY on the ICa reappeared in a time-dependent fashion. GTP or .alpha.-subunit perfused separately was relatively ineffective. The effects of NPY reappeared more rapidly at higher concentrations of .alpha.o. Chronic treatment of these cells with phorbol ester "down-regulates" protein kinase C (PKC) and reduces inhibition of the sustained current by NPY. In PTX-treated cells in which PKC had been removed by down-regulation, inhibition of ICa was also reconstituted following the perfusion of GTP/.alpha.o. Under these circumstances, NPY inhibited the transient phase of the ICa more than the sustained phase. These results indicte that Go, the major PTX substrate in the central nervous system, may normally mediate the inhibitory effects of NPY receptors on dorsal root ganglion Ca2+ channels.