title: In vitro aluminum inhibition of brain phosphoinositide metabolism: comparison of neonatal and adult rats.
abstract: 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.
authors.affiliation: Neurotoxicology Division, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Mundy
authors.forename: T
authors.initials: T
authors.lastname: Freudenrich
authors.forename: T J
authors.initials: TJ
authors.lastname: Shafer
authors.forename: A C
authors.initials: AC
authors.lastname: Nostrandt
mesh_terms: 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
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D007295:Inositol Phosphates; D000077410:Aluminum Chloride; D002217:Carbachol