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Evidence for direct and indirect mechanisms in the potent modulatory action of interleukin‐2 on the release of acetylcholine in rat hippocampal slices
Author(s) -
Seto David,
Kar Satyabrata,
Quirion Rémi
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701002
Subject(s) - acetylcholine , cholinergic , inhibitory postsynaptic potential , tetrodotoxin , hippocampal formation , long term potentiation , chemistry , receptor , stimulation , endocrinology , medicine , neuroscience , pharmacology , biology , biochemistry
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. 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. Tetrodotoxin (TTX; 10 μ m ) 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. In contrast, the inhibitory effect seen at a higher concentration (10 −9 m ) was TTX‐sensitive, and hence indicative of an indirect action. 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. Taken together, these results provide further evidence for the potent role of IL‐2 in the modulation of cholinergic function in the rat hippocampus.British Journal of Pharmacology (1997) 120 , 1151–1157; doi: 10.1038/sj.bjp.0701002