Effects of glucose and oxygen deprivation on phosphoinositide hydrolysis in cerebral cortex slices from neonatal rats.
The effects of glucose deprivation, hypoxia and glucose-free hypoxia conditions on phosphoinositide (PI) hydrolysis were studied in cortical slices from 8-day-old rats. Only glucose-free hypoxia induced a significant increase of inositol phosphate formation. The inositol phosphate formation induced by noradrenaline, carbachol and several excitatory amino acid receptor agonists, but not the Ca2+ ionophore A23187-induced stimulation, was blocked by glucose-free hypoxia and differentially reduced by glucose and oxygen deprivation depending on the neurotransmitter receptor agonist. The stimulatory effect of glucose-free hypoxia was not reduced by the muscarinic receptor antagonist atropine or by the inhibitors of the excitatory amino acid-stimulated PI hydrolysis DL-2-amino-3-phosphono-propionic acid and L-aspartate-beta-hydroxamate, and neither by the voltage-sensitive Na+ channel tetrodotoxin. The effect of glucose-free hypoxia was partially dependent on extracellular Ca2+ and it was blocked by verapamil and amiloride, but not by nifedipine, Co2+ and neomycin. These results suggest that Ca2+ influx through the Na(+)-Ca2+ exchanger underlies the PI hydrolysis stimulation induced by combined glucose and oxygen deprivation in neonatal cerebral cortical slices.
Cristòfol
R M
RM
Departamento de Farmacología y Toxicología, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Spain.
Rodríguez-Farré
E
E
Sanfeliu
C
C
D000818:Animals; D000831:Animals, Newborn; D000001:Calcimycin / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006868:Hydrolysis; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism; D019831:Sodium-Calcium Exchanger
D015220:Calcium Channels; D002352:Carrier Proteins; D010716:Phosphatidylinositols; D015221:Potassium Channels; D017470:Receptors, Glutamate; D019831:Sodium-Calcium Exchanger; D000001:Calcimycin; D019204:GTP-Binding Proteins; D005947:Glucose