Aluminum decreases muscarinic, adrenergic, and metabotropic receptor-stimulated phosphoinositide hydrolysis in hippocampal and cortical slices from rat brain.
Effects of aluminum chloride (AlCl3) (0.1 to 1000 microM) on inositol phosphate (IP) accumulation stimulated by carbachol (CARB), norepinephrine (NE) or quisqualate (QUIS) were examined in rat hippocampal and cortical slices. In the absence of agonist, only 1000 microM AlCl3 significantly reduced basal accumulation of IPs. For CARB-stimulated IP accumulation, 100 microM and greater AlCl3 significantly inhibited IP accumulation. In cortical slices, 1000 microM AlCl3 reduced CARB-stimulated IP accumulation by 55% and in hippocampal slices 1000 microM AlCl3 inhibited IP accumulation by 40%. Similar effects of AlCl3 were observed for NE-stimulated IP accumulation. In cortical slices, the concentration-response for AlCl3 effects on agonist-stimulated IP accumulation was significantly different from that in hippocampal slices. For QUIS-stimulated accumulation of IPs, 1000 microM AlCl3 significantly inhibited IP accumulation in hippocampal slices. However, in cortical slices a biphasic effect of AlCl3 was observed. 500 and 1000 microM AlCl3 significantly inhibited IP accumulation, whereas 10 and 50 microM AlCl3 significantly enhanced QUIS-stimulated IP accumulation. In both hippocampal and cortical slices, 500 microM AlCl3 significantly inhibited CARB-, NE- or QUIS-stimulated IP accumulation at all agonist concentrations (0.1 to 10000 microM) tested, indicating a post-receptor effect on agonist-mediated IP accumulation. Stimulation of G-proteins with NaF (5-30 mM) resulted in accumulation of IPs in hippocampal and cortical slices in the absence of added agonists. NaF (5-30 mM) plus 1 mM CARB produced increased accumulation of IPs over CARB or NaF alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Shafer
T J
TJ
Cellular and Molecular Toxicology Branch, United States Environmental Protection Agency, Research Triangle Park, NC 27711.
Mundy
W R
WR
Tilson
H A
HA
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D012969:Sodium Fluoride / Q000494:pharmacology
D017607:Aluminum Compounds; D002712:Chlorides; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011941:Receptors, Adrenergic; D017470:Receptors, Glutamate; D011976:Receptors, Muscarinic; D000077410:Aluminum Chloride; D016318:Quisqualic Acid; D002217:Carbachol; D012969:Sodium Fluoride; D009638:Norepinephrine