The combined effect of Pb2+ and Mn2+ on monoamine uptake and Na+, K+‐ATPase in striatal synaptosomes

Abstract

Rat striatal synaptosomes (P2-fraction) were subjected to lipoperoxidation by the addition of 120 microM Fe2+ and 200 microM ascorbic acid. This preparation (pretreated synaptosomes) was used to investigate the interaction of Pb2+ and Mn2+ on the uptake of tritiated catecholamines, Na+, K+-ATPase activity and malondialdehyde (MDA) formation in order to understand the mechanism of enhanced neurotoxicity by concurrent exposure to these metals. The combination of Pb2+ and Mn2+ (25 microM + 100 microM, respectively) produced a significant increase in the uptake of 3H-Dopamine only in the untreated synaptosomes. No significant effect was noted on the uptake of 3H-Norepinephrine in either pretreated or untreated synaptosomes. However, the combination of Pb2+ and Mn2+ produced a pronounced decrease in the activity of Na+, K+-ATPase, but the magnitude of the change was the sum of the individual metal effects. Metal interaction did not produce any significant change in the formation of MDA compared to the control (without addition of metals). These results indicate that Pb2+ and Mn2+ interaction may produce inhibition in the activity of transport ATPase in both the preparation of synaptosomes, with more pronounced effect of synaptosomes subjected to lipoperoxidation and these changes may be responsible for the disruption in the physiology of nerve impulse transmission.