Inhibitory effects of fucoidan on NMDA receptors and l-type Ca²⁺ channels regulating the Ca²⁺ responses in rat neurons

Abstract

Context: Fucoidan, a sulphated polysaccharide extracted from brown algae [Fucus vesiculosus Linn. (Fucaceae)], has multiple biological activities.

Objective: The effects of fucoidan on Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ responses of cortical neurons induced by AMPA or quisqualate. Meanwhile, the Ca²⁺ 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 Ca²⁺ channels, PR1/PR2.

Discussion and conclusions: Our data indicate that fucoidan suppresses the intracellular Ca²⁺ responses by selectively inhibiting NMDA receptors in cortical neurons and l-type Ca²⁺ channels in hippocampal neurons. A wide spectrum of fucoidan binding to cell membrane may be useful for designing a general purpose drug in future.

Keywords:

• Cortical and hippocampal neuron
• Ca²⁺ transient
• sulphated polysaccharide
• mRNA expression of PR1/PR2

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

The present work was mainly supported by the grant “Medical Photonics,” the 21st century Center of Excellence (COE: No. F13) from the Ministry of Education, Culture, Sports, Science and Technology, Japan and Collaborative Innovation Center of Henan University of Traditional Chinese Medicine, China.