The aim of the present experiments was to study the effects of the neurotransmitters acetylcholine, noradrenaline, 5-hydroxytryptamine, and dopamine on the Na+,K+-ATPase of rat brain synaptosomal fractions. It is shown that dopamine at low concentrations specifically inhibits the Na+,K+-ATPase of synaptic membranes from the brain regions rich in dopaminergic endings, but has no effect on the synaptosomal Na+,K+-ATPase from the other parts of brain. Acetylcholine and noradrenaline have similar specific effects on Na+,K+-ATPase from cholinergic and adrenergic synaptosomes. The Na+,K+-ATPase of synaptic membranes from the different brain regions, characterised by different distributions of cholinergic, adrenergic, and 5-hydroxytryptaminergic endings, show different reactions with neurotransmitters. These data indicate a functional significance of the effects of the neurotransmitters on the synaptosomal Na+,K+-ATPase.

Activity of the Na/K-ATPase from rat brain synaptic membranes is inhibited by NA (noradrenaline). However, during fractionation of cytozole from nerve endings, two non-homogeneous peaks are found (SF(a), 60-100 kD and SF( i ),;10 kD), which influence the Na/K-ATPase activity, both directly and SF(a) NA-dependently. Joint action of NA and synaptic factors (SF(a) and SF(i)) on the Na/K-ATPase, represents a sum of four different processes: 1) NA, without synaptic factors, inhibits the Na/K-ATPase; 2) At low SF(a) concentrations NA-dependent Na/K-ATPase activatory mechanism is evident; 3) At high SF(a) concentrations NA-independent Na/K-ATPase is activated; 4) The low-molecular SF(i) protein inhibits the Na/K-ATPase. Regulation of the Na/K-ATPase activity by NA, SF(a) and SF( i), obtained in similar conditions from two weeks old and one year old rats, is different. In older rats SF(i) is characterized with strong Na/K-ATPase inhibition; in younger rats SF(i) does not change the Na/K-ATPase activity. The NA- and SF(i) -dependent inhibition and activation ratio is different in young and elder rats. In two week olds NA/SF(i) activatory mechanism is stronger, while in one year olds NA-dependent inhibition of the Na/K-ATPase is prevailing. These experimental data indicate that regulation of the Na/K-ATPase activity has an important role in synaptic transmission and that this process has noteworthy, albeit presently unknown, functional importance in integrative activity of the brain.

Background The Na/K-ATPase activity of the brain synaptic plasma membranes (SPM) is regulated by noradrenaline (NA) and the synaptosomal factor SF (soluble protein obtained from the synaptosome cytosol). In the absence of SF, NA inhibits Na/K-ATPase, while, on addition of SF to the reaction medium, there is a NA-dependent activation of Na/K-ATPase . On the other hand, EGTA augments the Na/K-ATPase activity and attenuates the ability of NA to inhibit Na/K-ATPase. Results Considering that Ca 2+ ion is a Na/K-ATPase modifier, it can be assumed that the effect of NA and SF is a Ca 2+ -dependent process. However, in the presence of 0.3 mM EGTA and 0.1 mM NA, the apparent inhibition constant for Ca 2+ (at [Ca 2+ ] > 0.3 mM) is not SF dependent, while the apparent activation constant for SF does not change at increasing Ca 2+ concentration ([Ca 2+ ] < 0.3 mM). At various Ca 2+ concentrations (0.06, 0.35 and 0.6 mM), no significant changes occur in the mode of action of NA on the Na/K-ATPase activity in the presence of 5 μg/ml SF. EGTA also has no effect on the NA-independent activation of Na/K-ATPase evoked by high SF concentrations. Conclusions Taking into account that in the absence of EGTA similar results have been obtained, it can be concluded that the effect of NA and SF on brain Na/K-ATPase is a Ca 2+ -independent process.

Background: The Na/K-ATPase activity of the brain synaptic plasma membranes (SPM) is regulated by noradrenaline (NA) and the synaptosomal factor SF (soluble protein obtained from the synaptosome cytosol). In the absence of SF, NA inhibits Na/K-ATPase, while, on addition of SF to the reaction medium, there is a NA-dependent activation of Na/K-ATPase . On the other hand, EGTA augments the Na/K-ATPase activity and attenuates the ability of NA to inhibit Na/K-ATPase.