Evidence for direct and indirect mechanisms in the potent modulatory action of interleukin-2 on the release of acetylcholine in rat hippocampal slices

Abstract

1. The biphasic nature of the potent modulatory action of interleukin-2 (IL-2) on hippocampal acetylcholine (ACh) release was investigated by use of brain slice superfusion.

2. Both the potentiating (10⁻¹³ M) and inhibitory (10⁻⁹ M) effects of IL-2 on hippocampal ACh release were stimulation-dependent and were blocked by a neutralizing IL-2 receptor antibody, suggesting the activation of typical IL-2 receptors in both cases.

3. Tetrodotoxin (TTX; 10 μM) failed to block the potentiation of ACh release induced by a very low concentration of IL-2 (10⁻¹³M) suggesting a direct effect on cholinergic nerve terminals.

4. In contrast, the inhibitory effect seen at a higher concentration (10⁻⁹ M) was TTX-sensitive, and hence indicative of an indirect action.

5. To establish the nature of this intermediate mediator, blockers of nitric oxide synthesis, and of opioid and γ-aminobutyric acid (GABA) receptors were used. Only GABA_A and GABA_B receptor antagonists altered the inhibitory action of IL-2, suggesting the participation of GABA as mediator.

6. Taken together, these results provide further evidence for the potent role of IL-2 in the modulation of cholinergic function in the rat hippocampus.

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