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.
Johnson
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Department of Neurology, University of Alabama, Birmingham 35294.
Li
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Jope
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D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000535:Aluminum / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D012996:Solutions; D013268:Stimulation, Chemical; D013997:Time Factors
D017607:Aluminum Compounds; D002712:Chlorides; D012996:Solutions; D015762:2-Chloroadenosine; D005576:Colforsin; D000077410:Aluminum Chloride; D000535:Aluminum; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol