Evidence for direct and indirect mechanisms in the potent modulatory action of interleukin-2 on the release of acetylcholine in rat hippocampal slices.
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 microM) failed to block the potentiation of ACh release induced by a very low concentration of IL-2 (10(-13) M) 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 gamma-aminobutyric acid (GABA) receptors were used. Only GABAA and GABAB 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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Department of Pharmacology and Therapeutics, McGill University, Montréal, Québec, Canada.
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Quirion
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D018756:GABA Antagonists; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C052329:phaclofen; D013779:Tetrodotoxin; D001418:Baclofen; D000109:Acetylcholine; D001640:Bicuculline