Since calcium ion is known to be associated in the initiation of stimulus-induced neurotransmitter release from nerve endings, effects of imipramine and reserpine on the Nai--K+ ATPase, Mg++ATPase, Ca++_ Mg++ATPase and Na+-Ca´ ATPase activities in rat brain synaptosomes which may be associated with adrenoceptor were investigated.
In view of the possible role of mitochondria in the control of intracellular: Ca" concentration, suggested effects of imipramine and reserpine on the mitochondrial Ca++ uptake and the Na+-induced Ca´- release from -mitochondria were also studied.
Na+-K. ATPase activities in rat brain synaptosomes were inhibited by imipramine in a dose dependent manner. Reserpine, however showed no effect on or slightly increased these ATPase activities.
Na+-K` ATPase, Mg"ATPase and Ca"-Mg-+ATPase activities were all enhanced by norepinephrine and dopamine, but Na+-Ca++ATPase activity inhibited by these agents.
The effects of these catecholamines on these ATPase activities were antagonized by propranolol or yohimbine.
Imipramine inhibited all. the above mentioned ATPase activities in thesame degree in the presence or absence of the catecholamines. Reserpine decreased the effects of catecholamines on these ATPase activities. The initial rate of calcium binding to mitochondria was enhanced by imipramine, but the maximum calcium binding was not affected. In the presence of reserpine or verapamil, both the maximum calcium binding and the initial binding rate were inhibited.
With regard to Na+-induced Ca´ release from mitochondria, both the amount and rate. of calcium release were enhanced by imipramine, but were not altered by reserpine:
The above findings suggest that imipramine may increase the free intracellular calcium concentration through the inhibition of Na+-K+ATPase, Mg-++ATPase, Ca++_Mg++ATPase and Na´-Ca++ATPase activities which may result in enhancement of initial binding and subsequent release of Ca++ to and from mitochondria. On the other hand, reserpine may induce consistent release of neurotransmitters through the inhibition of the ATPase which may play a regulatory role in the release of neurotransmitters and it may maintain an increased intracellular free calcium by the inhibition of calcium binding to mitochondria.
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