||Aluminum Decreases Muscarinic, Adrenergic and Metabotropic Receptor-Stimulated Phosphoinositide Hydrolysis in Hippocampal and Cortical Slices from Rat Brain.
Shafer, T. J. ;
Mundy, W. R. ;
Tilson., H. A. ;
||Health Effects Research Lab., Research Triangle Park, NC. Neurotoxicology Div.
Cerebral cortex ;
Endogenous substance receptors ;
Adrenergic receptors ;
Muscarinic receptors ;
GTP-binding proteins ;
Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ;
Tissue distribution ;
Binding sites ;
Dose-response relationships ;
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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 micro M 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 1000 microM) tested, indicating a post-receptor effect on agonist-mediated IP accumulation. To determine the influence of the form of aluminum salt on IP accumulation, the effects of equimolar concentrations of AlCl3, aluminum citrate (Al(Cit)), and aluminum lactate (Al(Lac)) on CARB-stimulated IP accumulation were determined. Results suggest that: (1) AlCl3 disrupts IP accumulation mediated by different pharmacological classes of receptors; (2) differences in sensitivity to AlCl3 exist in the hippocampus and cortex; (3) AlCl3 and Al(4)F(-1)influence IP accumulation through separate mechanisms and Al(4)F(-1) is not responsible for effects of
AlCl3 on receptor-stimulated IP accumulation; (4) AlCl3 appears to exert its action on IP accumulation 'downstream' of the receptor and receptor-G-protein interaction; and (5) Effects of aluminum on IP accumulation are dependent upon the aluminum salts used.
||Pub. in Brain Research v629 n1 p133-140, 26 Nov 93.
|NTIS Title Notes
||Reprint: Aluminum Decreases Muscarinic, Adrenergic and Metabotropic Receptor-Stimulated Phosphoinositide Hydrolysis in Hippocampal and Cortical Slices from Rat Brain.
||PC A02/MF A01