IN-VITRO ALUMINUM INHIBITION OF BRAIN PHOSPHOINOSITIDE METABOLISM - COMPARISON OF NEONATAL AND ADULT-RATS

Recent evidence indicates that the neurotoxic metal aluminum interfere s with the phosphoinositide second messenger system in adult rats both in vitro and in vivo. We have examined the age-related effects of alu minum chloride (AICl(3)) 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 co rtex slices from 7 day old rats, decreased in 14 day old and 21 day ol d rats, and was lowest in adults (120 days old). AlCl3 (500 mu M) inhi bited both basal and carbachol-stimulated IP accumulation in neonatal and adult rats. The effects of AlCl3 were concentration-related and pr oduced significant decreases (15-25%) in IP accumulation at 500 and 1 000 mu M. The concentration-response curve for AlCl3 was similar in 7 day old and adult rats. AlCl3 reduced carbachol-, norepinephrine- and quisqualate-stim ulated IP accumulation in both 7 day old and adult ra ts. The effects of 500 mu M AlCl3 were examined on carbachol-stimulate d IP accumulation in slices prepared from frontal cortex, hippocampus, striatum, and cerebellum. Although IP accumulation was greater in sli ces from the 7 day old rats compared to adults in each tissue, AlCl3 ( 500 (m)u M) decreased IP accumulation by approximately 20% in all regi ons 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 alum inum decreases IP accumulation through a mechanism which is not age-de pendent. (C) 1995 Intox Press, Inc.