Inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in rat hippocampus by L-aspartate-beta-hydroxamate.
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-beta-hydroxamate was the most potent compound with the L-isomer (IC50 11 +/- 2 microM) being considerably more potent than the D-isomer (IC50 104 +/- 12 microM). The effect of the L-aspartate-beta-hydroxamate was found to be specific for ibotenate and quisqualate-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.
Ormandy
G C
GC
Biochemical Sciences, Wellcome Research Laboratories, Beckenham, U.K.
D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002217:Carbachol; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006868:Hydrolysis; D007051:Ibotenic Acid / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D005971:Glutamates; D010716:Phosphatidylinositols; C024848:beta-aspartylhydroxamic acid; D007051:Ibotenic Acid; D018698:Glutamic Acid; D001216:Asparagine; D002217:Carbachol