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ALUMINUM DECREASES MUSCARINIC, ADRENERGIC, AND METABOTROPIC RECEPTOR-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS IN HIPPOCAMPAL AND CORTICAL SLICES FROM RAT BRAIN
Citation:
Shafer, T., W. Mundy, AND H. Tilson. ALUMINUM DECREASES MUSCARINIC, ADRENERGIC, AND METABOTROPIC RECEPTOR-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS IN HIPPOCAMPAL AND CORTICAL SLICES FROM RAT BRAIN. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/201 (NTIS PB94163805).
Description:
Effects of aluminum chloride (AlCl3) (0.1 to 1000 um) on inositol phosphate (IP) accumulation stimulated by carbachol (CARB), norepinephrine (NE) or quisqualate (QUIS) were examined in rat hippocampal and cortical slices. n the absence of agonist, only 1000 um AIC1 significantly reduced basal accumulation of IPs. or CARB-stimulated PI accumulation, 50 uM and greater AlCl significantly inhibited IP accumulation. n cortical slices, 1000 uM AlCl, reduced CARB-stimulated IP accumulation by 55% and in hippocampal slice 1000 uM AlCl3, significantly inhibited IP accumulation by 40%. imilar effects of AlCl, were observed for NE-stimulated IP accumulation. n cortical slices, the concentration-response for AlCl, effects on agonist-stimulated IP accumulation was significantly different from that in hippocampal slices. or QUIS-stimulated accumulation of IPs, 1000 uM AlCl3, significantly inhibited IP accumulation in hippocampal slices. owever, in cortical-slices a biphasic effect of AlCl3, was observed. ive hundred and 1000 uM AlCl3 significantly inhibited IP accumulation, whereas 10 and 50 uM AlCl3, significantly enhanced QUIS-stimulated IP accumulation. n both hippocampal and cortical slices, 500 uM AlCl3 significantly inhibited CARB-, NE- or QUIS-stimulated IP accumulation at all agonist concentrations 0.1 to 10000 uM) tested, indicating a non-specific effect on receptor-mediated IP accumulation. timulation of G-proteins with NaF (5-30 MM) resulted in action of IPs in hippocampal and cortical slices in the absence of added agonists. aF (5-20 mM) plus 1 nM CARB produced increased accumulation IPs over CARB or NaF alone. lCL3 inhibited CARB- and NaF-stimulated IP accumulation, suggesting that AlCl3.