Inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in rat hippocampus by l-aspartate-β-hydroxamate

  • Ormandy G
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Abstract

The effect of a series of glutamate uptake inhibitors was tested on ibotenate-stimulated phosphoinositide hydrolysis. The pharmacological profile of the inhibitory effect of these compounds on the ibotenate response was quite different from that on glutamate uptake. Aspartate-β-hydroxamate was the most potent compound with the l-isomer (IC5011 ± 2 μM) beung considerably more potent than the d-isomer (IC50104 ± 12 μM). The effect of the l-aspartate-β-hydroxamate was found to be specific for ibotenate and quiqualate-stimulated phosphoinositide hydrolysis; this compound did not affect hydrolysis stimulated by carbachol, K+or sodium fluoride. The inhibition of the ibotenate response was found to involve a non-competitive and irreversible mechanism. © 1992.

Author-supplied keywords

  • Ibotenate
  • Phosphoinositide hydrolysis
  • l-Aspartate-β-hydroxamate

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Authors

  • George C. Ormandy

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