PMID- 1312458
OWN - NLM
STAT- MEDLINE
DCOM- 19920420
LR  - 20190813
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 33
IP  - 2
DP  - 1992 Mar-Apr
TI  - Excitatory amino acids modulate phosphoinositide signal transduction in human 
      epileptic neocortex.
PG  - 255-62
AB  - 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 (EC50: NE, 12 microM; Carb, 661 microM) as reflected by [3H]inositol 
      monophosphate (IP1) accumulation in tissue slices prelabeled with 
      [3H]myoinositol. These effects were dose-dependent, saturable, and five to six 
      times higher than basal IP1 accumulation. A weaker stimulation (twofold) was 
      observed with quisqualate (QUIS; EC50, 1.1 microM) and glutamate (GLU; EC50, 
      greater than 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 less than 0.05; Carb, -44%, 
      p less than 0.01). Preincubation of slices with various EEAs inhibited 
      Carb-induced IP1 formation. The maximal extent of inhibition (1 mM) was both 
      amino acid-dependent (IC50: NMDA, 5 microM; KA, 3.3 microM; QUIS, 47 microM; GLU, 
      greater than 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.
FAU - Dubeau, F
AU  - Dubeau F
AD  - Montreal Neurological Institute, Quebec, Canada.
FAU - Sherwin, A
AU  - Sherwin A
FAU - Olivier, A
AU  - Olivier A
FAU - Villemure, J
AU  - Villemure J
FAU - Leblanc, R
AU  - Leblanc R
FAU - Quesney, L F
AU  - Quesney LF
FAU - Andermann, E
AU  - Andermann E
FAU - Andermann, F
AU  - Andermann F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Glutamates)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Receptors, Neurotransmitter)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 8OC22C1B99 (Quisqualic Acid)
RN  - 8Y164V895Y (Carbachol)
RN  - SIV03811UC (Kainic Acid)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Carbachol/pharmacology
MH  - Cerebral Cortex/*metabolism/physiopathology
MH  - Dose-Response Relationship, Drug
MH  - Electroencephalography/methods
MH  - Epilepsy/*metabolism/physiopathology
MH  - Glutamates/pharmacology
MH  - Humans
MH  - Hydrolysis
MH  - In Vitro Techniques
MH  - Kainic Acid/pharmacology
MH  - N-Methylaspartate/pharmacology
MH  - Norepinephrine/pharmacology
MH  - Phosphatidylinositols/*metabolism
MH  - Quisqualic Acid/pharmacology
MH  - Receptors, Neurotransmitter/drug effects/metabolism
MH  - Second Messenger Systems/drug effects/physiology
MH  - Signal Transduction/*drug effects/physiology
EDAT- 1992/03/01 00:00
MHDA- 1992/03/01 00:01
CRDT- 1992/03/01 00:00
PHST- 1992/03/01 00:00 [pubmed]
PHST- 1992/03/01 00:01 [medline]
PHST- 1992/03/01 00:00 [entrez]
AID - 10.1111/j.1528-1157.1992.tb02314.x [doi]
PST - ppublish
SO  - Epilepsia. 1992 Mar-Apr;33(2):255-62. doi: 10.1111/j.1528-1157.1992.tb02314.x.