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 Mg(2+)-ATPase activities was investigated in homogenates of adult and aged rat whole brain at 37 degrees C. Adult and aged rat experiments were necessary in relation to phenylketonuria (PKU) since phenylketonuric patients usually discontinue their therapeutic special diet when they reach adulthood. Diet discontinuation results in the pathological increase of Phe concentration in plasma and consequently 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 brain Na(+), K(+)-ATPase was stimulated by 30--35% (P<0.01) in the presence of 0.48--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 homogenate for 3 h. Moreover, high Phe concentrations appeared unable to affect the activity of eel E. electricus pure AChE inhibited about 30% (P<0.001) by the free radical system H(2)O(2)/Fe(2+). Also, the antagonists of alpha- and beta-adrenergic receptors (phenoxybenzamine and propranolol, respectively) 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 brain Na(+), K(+)-ATPase are decreased with age; (b) These effects may be influenced by aging factors, such as free radical action and/or reduced density of alpha- and beta-adrenergic receptors in the tissue.
Tsakiris
S
S
Department of Experimental Physiology, University of Athens, Medical School, P.O. Box 65257, GR-154 01 Athens, Greece. stsakir@cc.uoa.gr
D000110:Acetylcholinesterase / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D017301:Ca(2+) Mg(2+)-ATPase; D004524:Eels; D005260:Female; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D010649:Phenylalanine / Q000378:metabolism* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D010643:Phenoxybenzamine; D010649:Phenylalanine; D011433:Propranolol; D000110:Acetylcholinesterase; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase