Modulation of hippocampal acetylcholine release: a potent central action of interleukin-2.
The potential of the T-cell growth factor interleukin-2 (IL-2) to modulate the release of ACh from rat hippocampus was studied in vitro, as a means to investigate the possible functional significance of this cytokine in the CNS. Hippocampal slices were superfused with Krebs' buffer medium, and endogenous ACh released into the superfusate was measured using a radioenzymatic assay. Recombinant human IL-2 present during a stimulation with 25 mM KCl altered, in a concentration-dependent manner, the evoked transmitter release. At a concentration of 15 U/ml (< or = 1 nM), IL-2 inhibited ACh release by more than 50% of the control level (evoked ACh release from the untreated contralateral hemispheres). Inhibition was observed within 20 min of tissue exposure to IL-2 and lasted for up to 1 hr. The inhibitory effect of IL-2 was reversible since transient tissue exposure to IL-2 did not affect subsequent evoked ACh release. IL-2 at this concentration also significantly decreased evoked ACh in frontal cortical slices, but was ineffective in the parietal cortex and striatum, revealing that IL-2 selectively modulates the release of ACh from certain, but not all, cholinergic nerve terminals in the CNS. At very low concentrations (1.5 mU/ml, < or = 0.1 pM), IL-2 transiently increased hippocampal evoked ACh release, resulting in a biphasic dose-response profile with no significant effect observed at 0.015 mU/ml (< or = 1 fM). Other cytokines (IL-1 alpha, IL-3, IL-5, IL-6, interferon alpha), tested in hippocampal slice incubations, failed to modulate ACh release.(ABSTRACT TRUNCATED AT 250 WORDS)
Hanisch
U K
UK
Douglas Hospital Research Centre, Department of Psychiatry, Montreal, Québec, Canada.
Seto
D
D
Quirion
R
R
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D011994:Recombinant Proteins; D011189:Potassium Chloride; D000109:Acetylcholine