Inhibitory Effect of Fangchinoline on Excitatory Amino Acids. Induced Neurotoxicity in Cultured Rat Cerebellar Granule Cells

  • Kim, Su-Don (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chunkbuk National University) ;
  • Oh, Sei-Kwan (College of Medicine, Ewha Womans Univeristy) ;
  • Kim, Hack-Seang (College of Pharmacy, Chungbuk National University) ;
  • Seong, Yeon-Hee (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chunkbuk National University)
  • Published : 2001.04.01

Abstract

Glutamate receptors-mediated excitoxicity is believed to play a role in the pathophysiology of neurodegenerative diseases. The present study was performed to evaluate the inhibitory effect of fanschinoline, a bis-benzylisoquinoline alkaloid, which has a characteristic as a $Ca^{2+}$channel blockers on excitatory amino acids (EAAS)-induced neurotoxicity in cultured rat cerebellar granule neuron. Fangchinoline (1 and 5$\mu\textrm{m}$) inhibited glutamate (1 ${m}M$), N-methyl-D-aspartate (NMDA; 1 ${m}M$) and kainate (100$\mu\textrm{m}$)-induced neuronal cell death which was measured by trypan blue exclusion test. Fangchinoline (1 and 5$\mu\textrm{m}$) inhibited glutamate release into medium induced by NMDA (1 ${m}M$) and kainate (100$\mu\textrm{m}$), which was measured by HPLC. And fangchinoline (5$\mu\textrm{m}$) inhibited glutamate (1 ${m}M$)-induced elevation of intracellular calcium concentration. These results suggest that inhibition of $Ca^{2+}$influx by fangchinoline may contribute to the beneficial effects on neurodegenerative effect of glutamate in pathophysiological conditions.

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