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 microM) had no effect on the cyclic AMP concentration in the absence of drugs that stimulate the synthesis of cyclic AMP. 2-Chloroadenosine (25-200 microM) significantly stimulated the synthesis of cyclic AMP in a concentration-dependent manner, and AlCl3 significantly potentiated this response at 50 and 100 microM 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) microM 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.