Reduction of phosphoinositide hydrolysis by L-amino-3-phosphonopropionate may be caused by the inhibition of synthesis of phosphatidylinositols.
L-Amino-3-phosphonopropionate (L-AP3), a putative antagonist of metabotropic glutamate receptors, inhibited the formation of [3H]inositol phosphates induced by (1S,3R)1-aminocyclopentane-1,3-dicarboxylic acid in rat hippocampal slices. The inhibition was accompanied by a decrease in the levels of [3H]phosphatidylinositols ([3H]PIs). Preincubation of slices with L-AP3 inhibited the incorporation of [3H]myo-inositol into PI fractions. The effects of L-AP3 was in contrast with those of a typical receptor antagonist, atropine; atropine inhibited carbachol-induced phosphoinositide hydrolysis, but the levels of [3H]PIs were not affected. These findings suggest that the inhibition of phosphoinositide hydrolysis by L-AP3 is not due to the receptor antagonism but may be caused by the inhibition of synthesis of PIs.
Ikeda
M
M
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D003864:Depression, Chemical; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D010716:Phosphatidylinositols / Q000096:biosynthesis* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D010716:Phosphatidylinositols; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D007294:Inositol; D001285:Atropine; D002217:Carbachol; D018021:Lithium Chloride; D000409:Alanine