The presynaptic a-adrenoceptors mediate a negative feedback mechanism which leads to inhibition of neurotransmitter release probably by restricting the calcium available for the excitation-secretion coupling. It is reported that norepinephrine may shorten the duration of plateau phase in action potential by,decreasing a voltage sensitive, slow inward calcium current and this action of norepinephrine is antagonized by u-adrenergic blocking agents. It is also suggested that there is a direct linkage between adrenoceptors and Na´-K´ ATPase.
In the present study, therefore, effects of norepinephrine, dopamine and 5-hydroxytryptamine on the calcium uptake, Na --Ca´´ exchange and membrane potential in rat brain synaptosomes were investigated. The actions of neurotransmitters on the regulators for cellular calcium transport were also studied` by investigating effects of catecholamines on synaptosomal Na+ -K + -ATPase, Mg´ + ATPase, Ca+´ ATPase and Na--Ca++ ATPase activities with or without adrenergic blocking agents. ,
In the reaction mixture containing calcium without potassium, the addition of ATP induced the synaptosomal calcium uptake only slightly. The further addition of potassium is followed by a marked increase in calcium uptake with concomittent development of membrane depolarization. Amounts of calcium uptake were increased with increasing concentrations of potassium but decreased in the presence of extracellular sodium.
Norepinephrine, dopamine and 5-hydroxytryptamine inhibited the potassium induced calcium uptake but had no effect on membrane potential. Na+-K´ ATPase, Mg+´ ATPase and Ca+ + ATPase activities were stimulated by these amines and stimulatory effects of catecholamines were antagonized by phentolamine and propranolol. Ouabain enhanced potassium induced calcium uptake but significantly inhibited Na+_K+ :ATPase activity. Diltiazem and dibucaine effectively inhibited the depolarization induced calcium uptake,
but had a variable effects on ATPase activities. Dibucaine significantly inhibited Ca+ + ATPase. Among various agents tested, dibucaine alone was shown to slow down the development of membrane depolarization,
Norepinephrine. dopamine and 5-hydroxytryptamine inhibited both the sodium dependent calcium efflux and Na+-Ca- ATPase activity. The inactivation of Na= -Ca+ + ATPase by catecholamines was reversed by phentolamine and propranolol.
These results suggest that there is a linkage between presynaptic adrenoceptors and regulatory apparatus for calcium transport across the synaptic membrane. Catecholamines appear to inhibit the calcium transport by the indirect effect on the ATPases, particulary Na+-K+ ATPase at plasma membrane which is mediated *To whom all correspondences should be addressed.
by adrenoceptors and also by possible action on the calcium conductance mechanism. On the otheri hand, adrenergic agonists may affect the Na+ dependent Ca+ + efflux in synaptic membranes.
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