Aluminum decreases muscarinic, adrenergic, and metabotropic receptor-stimulated phosphoinositide hydrolysis in hippocampal and cortical slices from rat brain

Abstract

Effects of alumiinum chloride (AlCl 3)(0.1 to 1000 μM) 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 μM AlCl 3 significantly reduced basal accumulation of IPs. For CARB-stimulated IP accumulation, 100 μM and greater AlCl 3 significantly inhibited IP accumulation. In cortical slices, 1000 μM AlCl 3 reduced CARB-stimulated IP accumulation by 55% and in hippocampal slices 1000 μM AlCl 3 inhibited IP accumulation by 40%. Similar effects of AlCl 3 were observed for NE-stimulated IP accumulation. In cortical slices, the concentration-response for AlCl 3 effects on agonist-stimulated IP accumulation was significantly different from that in hippocampal slices. For QUIS-stimulated accumulation of IPs, 1000 μM AlCl 3 significantly inhibited IP accumulation in hippocampal slices. However, in cortical slices a biphasic effect of AlCl 3 was observed. 500 and 1000 μM AlCl 3 significantly inhibited IP accumulation, whereas 10 and 50 μM AlCl 3 significantly enhanced QUIS-stimulated IP accumulation. In both hippocampal and cortical slices, 500 μM AlCl 3 significantly inhibited CARB-, NE- or QUIS-stimulated IP accumulation at all agonist concentrations (0.1 to 10000 μM) 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. AlCl 3 inhibited CARB- and NaF-stimulated IP accumulation, suggesting that AlCl 3 decreases IP accumulation by inhibiting G-protein or phospholipase C (PLC) activity. To determine the influence of the form of aluminum salt on IP accumulation, the effects of equinolar concentrations of AlCl 3, aluminum citrate (Al(Cit)), and aluminum lactate (Al(Lac)) on CARB-stimulated IP accumulation were determined. AlCl 3 and Al(Lac) produced similar inhibition of IP accumulation, whereas Al(Cit) did not inhibit receptor-stimulated IP accumulation. These results suggest that: (1) AlCl 3 disrupts IP accumulation mediated by different pharmacological classes of receptors; (2) differences in sensitivity to AlCl 3 exist in the hippocampus and cortex; (3) AlCl 3 and AlF − 4 influence IP accumulation through separate mechanisms and AlF − 4 is not responsible for effects of AlCl 3 on receptor-stimulated IP accumulation; (4) AlCl 3 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.