Korean J Physiol Pharmacol.
1998 Feb;2(1):41-48.
Differential effect of homocysteic acid and cysteic acid on changes of inositol phosphates and (Ca2+)i in rat cerebellar granule cells
- Affiliations
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- 1Department of Pharmacology, College of Medicine, Ewha Womans University, Seoul 158-056, Korea.
- 2Division of Neuroscience, Medical Research Center, Ewha Womans University, Seoul 158-056, Korea.
Abstract
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The present study was undertaken to characterize homocysteic acid
(HCA)-and cysteic acid (CA)mediated formation of inositol phosphates
(InsP) in primary culture of rat cerebellar granule cells. HCA and CA
stimulated InsP formation in a dose-dependent manner, which was
prevented by the N-methyl-D-aspartate (NMDA) receptor antagonist
D,L-2-amino-5-phosphopentanoic acid (APV). CA-, but not HCA-, mediated
InsP formation was in part prevented by the metabotropic glutamate
receptor antagonist alpha-methyl-4-carboxyphenylglycine ((+/-)-MCPG).
Both HCA- and CA-mediated increases in intracellular calcium
concentration were completely blocked by APV, but were not altered by
(+/-)-MCPG. CA-mediated InsP formation was in part prevented by removal
of endogenous glutamate. In contrast, the glutamate transport blocker
L-aspartic acid-beta-hydroxamate synergistically increased CA
responses. These data indicate that in cerebellar granule cells HCA
mediates InsP formation wholly by activating NMDA receptor. In
contrast, CA stimulates InsP formation by activating both NMDA receptor
and metabotropic glutamate receptor, and in part by releasing
endogenous glutamate into extracellular milieu.