a Laboratory of Cell Imaging , Henan University of Chinese Medicine , Zhengzhou , China.
b Photon Medical Research Center , Hamamatsu University School of Medicine , Hamamatsu , Japan.
Pharm Biol. 2019 Dec;57(1):1-7. doi: 10.1080/13880209.2018.1548626.
Fucoidan, a sulphated polysaccharide extracted from brown algae [Fucus vesiculosus Linn. (Fucaceae)], has multiple biological activities.
The effects of fucoidan on Ca responses of rat neurons and its probable mechanisms with focus on glutamate receptors were examined.
The neurons isolated from the cortex and hippocampi of Wistar rats in postnatal day 1 were employed. The intracellular Ca responses triggered by various stimuli were measured in vitro by Fura-2/AM. Fucoidan at 0.5 mg/mL or 1.5 mg/mL was applied for 3 min to determine its effects on Ca responses. RT-PCR was used to determine the mRNA expression of neuron receptors treated with fucoidan at 0.5 mg/mL for 3 h.
The Ca responses induced by NMDA were 100% suppressed by fucoidan, and those induced by Bay K8644 90% in the cortical neurons. However, fucoidan has no significant effect on the Ca responses of cortical neurons induced by AMPA or quisqualate. Meanwhile, the Ca responses of hippocampal neurons induced by glutamate, ACPD or adrenaline, showed only a slight decrease following fucoidan treatment. RT-PCR assays of cortical and hippocampal neurons showed that fucoidan treatment significantly decreased the mRNA expression of NMDA-NR1 receptor and the primer pair for l-type Ca channels, PR1/PR2.
Our data indicate that fucoidan suppresses the intracellular Ca responses by selectively inhibiting NMDA receptors in cortical neurons and l-type Ca channels in hippocampal neurons. A wide spectrum of fucoidan binding to cell membrane may be useful for designing a general purpose drug in future.
褐藻岩藻聚糖硫酸酯是一种从褐藻(Fucus vesiculosus Linn.(Fucaceae))中提取的硫酸多糖,具有多种生物学活性。
研究岩藻聚糖硫酸酯对大鼠神经元钙反应的影响及其可能的机制,重点关注谷氨酸受体。
采用出生后第 1 天 Wistar 大鼠皮质和海马神经元进行体外实验。通过 Fura-2/AM 测量各种刺激引发的细胞内钙反应。将岩藻聚糖硫酸酯分别以 0.5mg/mL 或 1.5mg/mL 作用 3 分钟,检测其对钙反应的影响。用 RT-PCR 检测岩藻聚糖硫酸酯作用 3 小时后神经元受体的 mRNA 表达。
岩藻聚糖硫酸酯可完全抑制皮质神经元 NMDA 诱导的钙反应,90%抑制 Bay K8644 诱导的钙反应;但对皮质神经元 AMPA 或 quisqualate 诱导的钙反应无明显影响。同时,岩藻聚糖硫酸酯对谷氨酸、ACPD 或肾上腺素诱导的海马神经元钙反应仅有轻微抑制作用。皮质和海马神经元的 RT-PCR 检测显示,岩藻聚糖硫酸酯处理可显著降低 NMDA-NR1 受体和 l 型钙通道 PR1/PR2 的 mRNA 表达。
本研究数据表明,岩藻聚糖硫酸酯通过选择性抑制皮质神经元 NMDA 受体和海马神经元 l 型钙通道,抑制细胞内钙反应。岩藻聚糖硫酸酯与细胞膜的广泛结合可能有助于未来设计通用药物。