Effect of amino acid ergot alkaloids on glutamate transport via human glutamate transporter hGluT-1.
Journal: 1998/August - Journal of the Neurological Sciences
ISSN: 0022-510X
PUBMED: 9562319
Abstract:
Effect of amino acid ergot alkaloids on glutamate transport via the human glutamate transporter (hGluT-1) was investigated using hGluT-HeLaS3 cells, which stably expressed high levels of hGluT-1. Ergotamine enhanced the glutamate uptake of hGluT-HeLaS3 cells in a concentration-dependent manner, increasing the initial velocity of glutamate uptake by 1.45 times at 10 microM. Other amino acid alkaloids, bromocriptine and dihydroergotamine, also augmented glutamate uptake, whereas amine alkaloids, ergonovine or lisuride did not influence glutamate uptake. The accelerating effect required a preincubation longer than 5 min. Kinetic studies on hGluT-1 revealed that ergot alkaloids decreased a Michaelis constant (Km) for glutamate with unchanged maximum velocity. The effect of bromocriptine was not mediated by dopamine D1 or D2 receptors, and was independent of its antioxidant action. Amino acid ergot alkaloids may serve as a prototype for agents that regulate glutamate transporters. These results may be useful in exploring new agents for neurological diseases associated with glutamatergic neurotoxicity.
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