Aluminum Increases Agonist‐Stimulated Cyclic AMP Production in Rat Cerebral Cortical Slices

The effects of AlCl₃ on basal and stimulated cyclic AMP production in rat cerebral cortical slices were studied. AlCl₃ (10-250 μM) had no effect on the cyclic AMP concentration in the absence of drugs that stimulate the synthesis of cyclic AMP. 2-Chloroadenosine (25-200 μM) significantly stimulated the synthesis of cyclic AMP in a concentration-dependent manner, and AlCl₃ significantly potentiated this response at 50 and 100 μM 2-chloroadenosine. This effect of AlCl₃ was dependent on preexposure of the slices to AlCl₃ before addition of the agonist. The potentiation by AlCl₃ of the 2-chloroadenosine-induced increase in cyclic AMP level was concentration dependent, with significant enhancement by 100 (142% of the control) and 250 (150% of the control) μM AlCl₃. Lower concentrations of AlCl₃ had no significant effect on the production of cyclic AMP stimulated by 2-chloroadenosine. AlCl₃ also potentiated the isoproterenol-induced increase in cyclic AMP production. Forskolin-induced production of cyclic AMP was unaltered by the presence of AlCl₃. These results demonstrate that AlCl₃ can potentiate agonist-stimulated cyclic AMP production in a whole-cell brain preparation without the addition of fluoride. This may account for the previously reported aluminum-induced increase in cyclic AMP concentrations in rat brain in vivo.