In vitro aluminum inhibition of brain phosphoinositide metabolism: comparison of neonatal and adult rats.
Recent evidence indicates that the neurotoxic metal aluminum interferes with the phosphoinositide second messenger system in adult rats both in vitro and in vivo. We have examined the age-related effects of aluminum chloride (AlCl3) on receptor-stimulated inositol phosphate (IP) accumulation in brain slices from neonatal and adult rats in vitro. Carbachol-stimulated (1 mM) IP accumulation was greatest in frontal cortex slices from 7 day old rats, decreased in 14 day old and 21 day old rats, and was lowest in adults (120 days old). AlCl3 (500 microM) inhibited both basal and carbachol-stimulated IP accumulation in neonatal and adult rats. The effects of AlCl3 were concentration-related and produced significant decreases (15-25%) in IP accumulation at 500 and 1000 microM. The concentration-response curve for AlCl3 was similar in 7 day old and adult rats. AlCl3 reduced carbachol-, norepinephrine- and quisqualate-stimulated IP accumulation in both 7 day old and adult rats. The effects of 500 microM AlCl3 were examined on carbachol-stimulated IP accumulation in slices prepared from frontal cortex, hippocampus, striatum, and cerebellum. Although IP accumulation was greater in slices from the 7 day old rats compared to adults in each tissue, AlCl3 (500 microM) decreased IP accumulation by approximately 20% in all regions at both ages. Aluminum produced concentration-dependent inhibition of phospholipase C in cortical homogenates which was similar in 7 day old and adult rats. These results show that in vitro exposure to aluminum decreases IP accumulation through a mechanism which is not age-dependent.
Mundy
W R
WR
Neurotoxicology Division, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Freudenrich
T
T
Shafer
T J
TJ
Nostrandt
A C
AC
D000367:Age Factors; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D051381:Rats
D017607:Aluminum Compounds; D002712:Chlorides; D007295:Inositol Phosphates; D000077410:Aluminum Chloride; D002217:Carbachol