[Role of Na and Cl ions in retaining noradrenaline and serotonin in the meso-diencephalic region of the rat brain and in the action of gamma-aminobutyric acid on that process]. / Znachenie ionov Na i Cl v uderzhivanii noradrenalina i serotonina v mezo-díentsefalicheskoi oblasti mozga krys i v deistvii gamma-aminomaslianoi kisloty na étot

It has been previously reported from this laboratory that CABA affects the retention of norepinephrine (NE) and serotonin (5-HT) in rat brain tissue [2, 3, 4]. The addition of GABA (100 mug/ml) to the incubation medium enhances significantly the loss of NE from slices while the loss of 5-HT is, on the contrary, significantly smaller than that observed from slices incubated parallely for the same period. It has also been shown that this effect is observed only in a balanced ionic medium [1]. With the purpose of finding out the importance of Na+ and Cl- ions in the storage of monoamines and in the effect of GABA on this process in the present report we studied the effect of GABA on the loss of NE and 5-HT from slices of rat mesodiencephalic region incubated in media free of Na+ and Cl- ions. The effect of GABA on Na+, K+-ATP-ase activity, an enzyme involved in the active transport of monoamines, was also studied. The results obtained indicate that loss of both NE and 5-HT from slices was significantly enhanced in a Na+-free medium and that on addition of GABA (100 mug/ml) to such a medium no significant changes GABA were noted. In a Cl--free medium loss of NE from slices was enhanced while that of 5-HT was not affected. When GABA was added to such a medium the usual pattern so far observed in our experiments, i.e. an enhancement in the loss of NE from slices, was found to be reversed. The pronounced decrease of NE observed in a Cl--free medium was found to be partially checked by the addition of GABA, the difference observed being statistically significant. Thus, in a Cl--free medium GABA seems to display an effect on NE storage opposite to that observed in a normal medium. Incubation in a Cl--free medium did not induce any noticeable change in the retention of 5-HT in slices. However, when GABA was added to slices incubated in a Cl--free medium, it no more displayed its usual effect, i.e. it did not inhibit the loss of 5-HT from slices. Under the given experimental conditions, GABA added to a balanced ionic medium did not effect Na+,K+-ATP-ase activity. This is in good agreement with previous results from our laboratory [4] where GABA was shown to have no effect on the uptake of NE and 5-HT by slices of rat brain, an active, carrier-mediated process coupled with Na+,K+-ATP-ase activity.

[Effect of gamma-aminobutyric acid and noradrenaline on the ATPase activity of rat brain tissue]. / Vliianie gamma-aminomaslianoi kisloty i noradrenalina na ATF-aznuiu aktivnost' mozgovoi tkani krys

Inasmuch as the highest concentrations of transmitter substances occur in the mesodiencephalic region of the brain, which according to our results possesses quite high Na+,K+-ATP-ase activity, in the present study we tried the effect of norepinephrine (NE) and gamma-aminobutyric acid (GABA) on Na+, K+-ATP-ase activity of rat mesodiencephalic region. The results obtained indicate that in homogenates NE (5-10(-4) M) stimulates Na+, K+-ATP-ase activity about 3.6 times, while equimolar amounts of GABA have no effect. Higher concentrations of GABA (1.10(-3) M and 3.10(-3) M), as well as changes in the length of the preincubation period with GABA, failed to affect enzyme activity. Effect of transmitters was next studied on ATP-ase activity of synaptosomal fractions of the mesodiencephalic region. Here also a statistically significant increase of enzyme activity was observed from NE but not from GABA. Changes in ATP-ase activity of rat brain synaptosomal fractions were also not observed in in vivo studies 20 min after i.p. administrations of 5 mg/kg GABA. The results of the present study indicate that NE stimulates Na+, K+-ATP-ase activity of rat brain mesodiencephalic region while under the given experimental conditions GABA does not seem to have any effect.

[Effect of gamma-aminobutyric acid on the concentration of noradrenaline in the synaptosoma fraction of the meso-diencephalic region of rat brain]. / Deistvie gamma-aminomaslianoi kisloty na soderzhanie noradrenolina v sinaptosomal'noi fraktsii mezo-diéntsefalicheskoi oblasti mozga krys.

We had previously shown [1, 2, 3, 4] that intraperitoneal administrations of 5 mg/kg amounts of gamma-aminobutyric acid (GABA) lower norepinephrine (NE) level of rat brain, this effect being most pronounced in the hypothalamic region. Subsequent studies showed that GABA increased normetanephrine level in iproniazid pretreated rats (II) and decreased NE content of crude mitochondrial fractions (12). These data implied changes in NE content of nerve endings. The results of the present study indicate that the NE content of the synaptosomal fraction of the mesodiencephalic region of GABA treated rats is significantly lower than that of untreated animals. This is a further confirmation of our previous results favouring a release of NE from nerve endings following the administration of GABA.