Effects of (-)deprenyl (selegiline) on acetylcholinesterase and Na(+),K(+)-ATPase activities in adult rat whole brain.
(-)Deprenyl is an irreversible inhibitor of monoaminoxidase-B (MAO-B) at concentration 10(-6)M and of both MAO-A and MAO-B at concentration 10(-5)M. In this study, the effect of different concentrations (10(-7)-10(-4)M) of (-)deprenyl on the activity of acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase was investigated in homogenates of adult rat whole brain and in pure enzymes. Drug preincubation period with the homogenates or pure enzymes was 1 and 3h. Brain AChE activity was decreased by 30-39% (P<0.01) when exposed to 10(-4)M (-)deprenyl, by 22-25% (P<0.01) when exposed to 10(-5)M of the drug, and by 18-20% (P<0.01) after preincubation with a concentration of the drug 10(-6)M. Brain Na(+),K(+)-ATPase was stimulated by 46-162% (P<0.001) when the homogenate was preincubated with 10(-4)M (-)deprenyl and by 36-104% (P<0.001) for preincubation with drug concentration 10(-6)M. No effect was observed on the activity of brain Mg(2+)-ATPase, pure AChE or pure Na(+),K(+)-ATPase when exposed to the above concentrations of the drug. We conclude that (-)deprenyl is an indirect AChE inhibitor and Na(+),K(+)-ATPase stimulator in the rat brain (in vitro).
Antoniades
Charalambos
C
Department of Experimental Physiology, Medical School, University of Athens, P.O. Box 65257, GR-154 01 Athens, Greece.
Carageorgiou
Haris
H
Tsakiris
Stylianos
S
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D004593:Electrophorus; D066298:In Vitro Techniques; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D012642:Selegiline / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
D018696:Neuroprotective Agents; D012642:Selegiline; D000110:Acetylcholinesterase; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase