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Excitatory Amino Acids Modulate Phosphoinositide Signal Transduction in Human Epileptic Neocortex
Author(s) -
Dubeau F.,
Sherwin A.,
Olivier A.,
Villemure J.,
Leblanc R.,
Quesney L. F.,
Andermann E.,
Andermann F.
Publication year - 1992
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1992.tb02314.x
Subject(s) - neocortex , kainate receptor , nmda receptor , glutamate receptor , stimulation , epileptogenesis , medicine , kainic acid , endocrinology , receptor , chemistry , agonist , biology , excitatory postsynaptic potential , neuroscience , ampa receptor , biochemistry , hippocampus
Summary: Stimulation of phosphoinositide (PI) hydrolysis by norepinephrine (NE), carbachol (Carb), and excitatory amino acids (EAAs) was measured in slices prepared from neocortex excised during epilepsy surgery. NE and Carb markedly enhanced PI turnover (EC 50 : NE, 12 μM; Carb, 661 μM) as reflected by [ 3 H]inositol monophosphate (IP 1 ) accumulation in tissue slices prelabeled with [ 3 H]myoinositol. These effects were dose‐dependent, saturable, and five to six times higher than basal IP 1 accumulation. A weaker stimulation (twofold) was observed with quisqualate (QUIS; EC 50 , 1.1 μM) and glutamate (GLU; EC 50 , >1 mM), while minimal or no stimulation was seen with kainate (KA) and N‐methyl‐D‐aspartate (NMDA). Agonist‐stimulated PI turnover was significantly reduced in samples from actively spiking epileptic neocortex versus nonspiking areas as defined by electrocorticography (NE, ‐23%, p < 0.05; Carb, ‐44%, p < 0.01). Preincubation of slices with various EEAs inhibited Carb‐induced IP 1 formation. The maximal extent of inhibition (1 mM) was both amino acid‐(NMDA > KA > QUIS > GLU) and concentration‐dependent (IC 50 : NMDA, 5 μM; KA, 3.3 μM; QUIS, 47 μM; GLU, > 1 mM). These data suggest that epileptic activity modulates PI metabolism and alters receptor‐effector coupling. As important mediators of epileptogenesis, EAAs may interfere with the efficiency of this second messenger system.