Effects of L-phenylalanine on acetylcholinesterase and Na+, K+-ATPase activities in adult and aged rat brain

The effect of different L-phenylalanine (Phe) concentrations (0.12-1.8 mM) on acetylcholinesterase (AChE), (Na+, K+)-ATPase and Mg2+-ATPase activities was investigated in homogenates of adult and aged rat whole brain at 37 de greesC. Adult and aged rat experiments were necessary in relation to phenyl ketonuria (PKU) since phenylketonuric patients usually discontinue their th erapeutic special diet when they reach adulthood. Diet discontinuation resu lts in the pathological increase of Phe concentration in plasma and consequ ently in brain. AChE activity in adult brain homogenates showed a decrease up to 18%, (P < 0.01) with 0.48-1.8 mM Phe preincubated for 1 h. Adult brai n Na+, K+-ATPase was stimulated by 30-35% (P < 0.01) in the presence of 0.4 8-1.8 mM Phe. However, high Phe concentrations were not able to affect the activities of AChE and Na+, K+-ATPase, when preincubated with aged brain ho mogenate for 3 h. Moreover, high Phe concentrations appeared unable to affe ct the activity of eel E. electricus pure AChE inhibited about 30%, (P < 0. 001) by the free radical system H2O2/Fe2+. Also, the antagonists: of <alpha >- and beta -adrenergic receptors (phenoxybenzamine and propranolol. respec tively) inhibited adult rat brain Na+, K+-ATPase activity about 30-40% (P < 0.01) and Phe was unable to change this action. It is suggested that: (a) The inhibitory effect of Phe on brain AChE and its stimulatory effect on br ain Na+, K+-ATPase are decreased with age; (b) These: effects may be influe nced by aging factors, such as free radical action and/or reduced density o f <alpha>- and beta -adrenergic receptors in the tissue. (C) 2001 Elsevier Science Ireland Ltd, All rights reserved.