omega-Conotoxin GVIA (omega-CT) diminished the potassium-induced in vitro release of 3H-gamma-aminobutyric acid (3H-GABA) from slices of rat neostriatum in a manner which depended on the concentration of potassium. omega-CT (0.1 mmol/l) decreased the release of 3H-GABA induced by 25 mmol/l K+ from 11.6% to 6.1% of tissue content, ie. by 48%, while it did not affect the release of 3H-GABA caused by 20 mmol/l K+, which was 4.8% of tissue content. However, in the presence of a polyclonal antiserum or cysteamine (600 mumol/l), both of which diminish the effects of endogenous somatostatin, 0.1-10 nmol/l omega-CT decreased the release of 3H-GABA induced by 20 mmoles/l K+ by 40%. It is concluded that omega-CT did not only inhibit GABA-neurones, but had an additional inhibitory effect on somatostatin neurones which are known to depress the release of 3H-GABA. It is further concluded that neuronal interactions, which are possible in brain slice preparations, may impede the interpretation of effects of drugs, especially if agents are used which affect basic mechanisms of transmitter release and thus the release of various transmitters from neurones.

Creatine has been used previously to alter the energy balance of neurons in brain slices. In the present experiments, it was found to reduce the accumulation of gamma-[3H]aminobutyric acid ([3H]GABA) as synthesized from [3H]glutamine or [3H]glutamic acid in slices of rat neostriatum. The lowest effective concentration was 5 mM. Creatine (25 mM) was also effective when the degrading enzyme of GABA, i.e., GABA-alpha-oxoglutarate transaminase, was blocked by gabaculine. Creatine (25 mM) did not inhibit the uptake and subsequent accumulation of [3H]GABA. Thus, indirect evidence was obtained that creatine decreased the activity of the synthesizing enzyme of GABA, i.e., glutamate decarboxylase. When the direct effect of creatine (25 mM) on glutamate decarboxylase was studied in vitro, the agent indeed decreased the activity of the enzyme. Creatine (25 mM) also diminished the release of [3H]GABA (expressed as dpm/mg wet weight) from rat neostriatal slices, probably by reducing its synthesis and thus its readily releasable pool. These data are of importance for studies with creatine in complex neuronal systems, because they show that the agent changes not only neuronal energy balance, but also synthesis and release of the ubiquitous transmitter GABA.

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