Inhibitory effect of NMDA receptor activation on quisqualate-stimulated phosphatidylinositol turnover in the human cerebral cortex.
The effect of excitatory amino acids (EAA) on the phosphatidylinositol (PI) turnover in human cerebral cortical slices was investigated. Quisqualic acid (QA) and, to lesser extent, ibotenic acid (IBO) at 10(-5)-10(-3) M increased inositol phosphate (IP) accumulation. L-Glutamic acid (L-glu), kainic acid (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartic acid (NMDA) were ineffective. NMDA dose-dependently antagonized the QA facilitatory effect. Such inhibition was prevented by the NMDA receptor complex antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d]cyclohepten-5,10-imine (MK-801) and by 3[+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid. The effect of IBO (but not that of QA) was greatly potentiated by MK-801. These data suggest that the EAA metabotropic receptor described in the rodent brain is also present in human cerebral cortex and is negatively modulated by the NMDA receptor.
Morari
M
M
Institute of Pharmacology, University of Ferrara, Italy.
Calo
G
G
Antonelli
T
T
Gaist
G
G
Acciarri
N
N
Fabrizi
A
A
Bianchi
C
C
Beani
L
L
D000596:Amino Acids / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007051:Ibotenic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010716:Phosphatidylinositols / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*
D000596:Amino Acids; D010716:Phosphatidylinositols; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; D016291:Dizocilpine Maleate; D016318:Quisqualic Acid; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid