INTERACTIONS BETWEEN PHOSPHOLIPASE C-COUPLED AND N-METHYL-D-ASPARTATE RECEPTORS IN CULTURED CEREBELLAR GRANULE CELLS - PROTEIN-KINASE-C MEDIATED INHIBITION OF N-METHYL-D-ASPARTATE RESPONSES
INTERACTIONS BETWEEN PHOSPHOLIPASE C-COUPLED AND N-METHYL-D-ASPARTATE RECEPTORS IN CULTURED CEREBELLAR GRANULE CELLS - PROTEIN-KINASE-C MEDIATED INHIBITION OF N-METHYL-D-ASPARTATE RESPONSES
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DOI：
10.1111/j.1471-4159.1992.tb08339.x
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发表时间：
1992-09-01
影响因子：
4.7
通讯作者：
NICHOLLS, DG
中科院分区：
文献类型：
--
作者：
COURTNEY, MJ;NICHOLLS, DG
磷脂酶C偶联受体激活抑制原代培养的大鼠小脑颗粒细胞的N-甲基-D-天冬氨酸（NMDA）受体。在不存在离子型激动剂的情况下，细胞调节其细胞质游离Ca 2+，[Ca 2 +]c，以响应通过各自的激动剂卡巴胆碱、反式-1-氨基-1，3-环戊烷二羧酸和内皮素-1刺激M3毒蕈碱受体、代谢型谷氨酸受体和内皮素受体。该反应与磷脂酶C偶联受体释放细胞内Ca 2+池并诱导随后的Ca 2+进入细胞的能力一致;这两种反应都可以通过用低浓度的离子霉素或毒胡萝卜素释放内部Ca 2+储存来消除。在用NMDA刺激的细胞的情况下，对磷脂酶C偶联激动剂的[Ca 2 +]c响应是复杂的和激动剂依赖性的;然而，在离子霉素的存在下，每种激动剂产生对[Ca 2 +]c信号的NMDA组分的部分抑制。这种抑制作用可以通过蛋白激酶C激活剂4-β-佛波醇12，13-二丁酸酯模拟。结论：小脑颗粒细胞上的NMDA受体通过激活蛋白激酶C被磷脂酶C偶联的毒蕈碱M3、谷氨酸能和内皮素受体抑制。
The N-methyl-D-aspartate (NMDA) receptor of rat cerebellar granule cells in primary culture is inhibited by phospholipase C-coupled receptor activation. In the absence of ionotropic agonist, cells modulate their cytoplasmic free Ca2+, [Ca2+]c, in response to stimulation of M3 muscarinic receptors, metabotropic glutamate receptors, and endothelin receptors by the respective agonists carbachol, trans-1-amino-1,3-cyclopentanedicarboxylic acid, and endothelin-1. The response is consistent with the ability of phospholipase C-coupled receptors to release a pool of intracellular Ca2+ and induce a subsequent Ca2+ entry into the cell; both of these responses can be abolished by discharge of internal Ca2+ stores with low concentrations of ionomycin or thapsigargin. In the case of cells stimulated with NMDA, the [Ca2+]c response to the phospholipase C-coupled agonists is complex and agonist dependent; however, in the presence of ionomycin each agonist produces a partial inhibition of the NMDA component of the [Ca2+]c signal. This inhibition can be mimicked by the protein kinase C activator 4-beta-phorbol 12,13-dibutyrate. It is concluded that NMDA receptors on cerebellar granule cells are inhibited by phospholipase C-coupled muscarinic M3, glutamatergic, and endothelin receptors via activation of protein kinase C.