Acetylcholine as a mitogen: Muscarinic receptor-mediated proliferation of rat astrocytes and human astrocytoma cells
Acetylcholine as a mitogen: Muscarinic receptor-mediated proliferation of rat astrocytes and human astrocytoma cells
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DOI：
10.1016/0014-2999(95)00746-6
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发表时间：
1996-02-22
影响因子：
5
通讯作者：
Costa, LG
中科院分区：
文献类型：
--
作者：
Guizzetti, M;Costa, P;Costa, LG
在大鼠皮质星形胶质细胞和人132 1N1星形细胞瘤细胞中，已经表征了毒蕈碱受体激动剂在神经胶质细胞中的促有丝分裂作用。毒蕈碱受体激动剂卡巴胆碱引起的增殖的剂量和时间依赖性增加，测量[H-3]胸苷掺入。有丝分裂的影响是模仿几个毒蕈碱，但不是烟碱受体激动剂，并被阻断毒蕈碱受体拮抗剂。逆转录-聚合酶链反应（RT-PCR）实验表明，在星形胶质细胞和星形细胞瘤细胞中存在M2，M3和在较小程度上，M5毒蕈碱受体mRNA。亚型特异性毒蕈碱受体拮抗剂的增殖实验表明，卡巴胆碱诱导的增殖是由于毒蕈碱M（3）受体的激活。佛波酯12-O-十四烷酰基-佛波醇13-乙酸酯（TPA）也刺激胶质细胞增殖。下调蛋白激酶C或蛋白激酶C拮抗剂1，5-（isoquinolynsulfanyl）-2-甲基哌嗪二盐酸盐（H7）阻断TPA或卡巴胆碱诱导的增殖。其他神经递质测试，组胺引起神经胶质细胞增殖，去甲肾上腺素和γ-氨基丁酸是无效的，而血清素和谷氨酸抑制基础或血清刺激的增殖。
The mitogenic effect of muscarinic receptor agonists in glial cells has been characterized in rat cortical astrocytes and human 132 1N1 astrocytoma cells. The muscarinic receptor agonist carbachol caused a dose- and time-dependent increase in proliferation, as measured by [H-3]thymidine incorporation. The mitogenic effect was mimicked by several muscarinic, but not nicotinic receptor agonists, and was blocked by muscarinic receptor antagonists. Reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated the presence of m2, m3 and to a lesser degree, m5 muscarinic receptor mRNA in both astrocytes and astrocytoma cells. Proliferation experiments with subtype-specific muscarinic receptor antagonists suggest that carbachol-induced proliferation is due to activation of muscarinic M(3) receptors. The phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) also stimulated glial cell proliferation. Down-regulation of protein kinase C, or the protein kinase C antagonist 1,5-(isoquinolynsulfanyl)-2-methylpiperazine dihydrochloride (H7) blocked proliferation induced by either TPA or carbachol. Of other neurotransmitters tested, histamine caused glial cell proliferation, norepinephrine and gamma-aminobutyric acid were ineffective, while serotonin and glutamate inhibited basal or serum-stimulated proliferation.