Inhibitory effects of fucoidan on NMDA receptors and l-type Ca(2+) channels regulating the Ca(2+) responses in rat neurons

Context: Fucoidan, a sulphated polysaccharide extracted from brown algae [Fucus vesiculosus Linn. (Fucaceae)], has multiple biological activities. Objective: The effects of fucoidan on Ca(2+) responses of rat neurons and its probable mechanisms with focus on glutamate receptors were examined. Materials and methods: The neurons isolated from the cortex and hippocampi of Wistar rats in postnatal day 1 were employed. The intracellular Ca(2+) 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(2+) responses. RT-PCR was used to determine the mRNA expression of neuron receptors treated with fucoidan at 0.5 mg/mL for 3 h. Results: The Ca(2+) 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(2+) responses of cortical neurons induced by AMPA or quisqualate. Meanwhile, the Ca(2+) 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(2+) channels, PR1/PR2. Discussion and conclusions: Our data indicate that fucoidan suppresses the intracellular Ca(2+) responses by selectively inhibiting NMDA receptors in cortical neurons and l-type Ca(2+) channels in hippocampal neurons. A wide spectrum of fucoidan binding to cell membrane may be useful for designing a general purpose drug in future.