Nitrergic modulation of hippocampal acetylcholine release is independent of endothelial NO synthase activity.
Nitric oxide (NO) is involved in hippocampal phenomena of synaptic plasticity. The present microdialysis study investigated a possible role of NO and of endothelial NO synthase (eNOS) activity in the control of hippocampal acetylcholine (ACh) release. 3-Morpholinosydnonimine (SIN-1), an NO donor, stimulated ACh release by 50%-70% when infused into the hippocampus of wild type C57B16 mice. Infusion of L-nitroarginine (L-NA), a broad-spectrum inhibitor of NO synthases, decreased hippocampal ACh efflux by approximately 50%. Mice lacking eNOS (eNOS knockouts) had identical basal effluxes of hippocampal ACh as wild type mice, and the responses to SIN-1 and L-NA were unchanged in the absence of eNOS activity. We conclude that nitric oxide (NO) stimulates hippocampal ACh release in a tonic fashion, but independently of eNOS activity.
Buchholzer
Marie-Luise
ML
Department of Pharmacology, Johannes Gutenberg University of Mainz, Mainz, Germany.
Klein
Jochen
J
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D000109:Acetylcholine