The NO synthase inhibitors L-Name and L-NMMA, but not L-arginine, block the mammalian nicotinic acetylcholine receptor channel.
(1) Nitric oxide (NO) synthase inhibitors (NOS-I) such as L-Name (N(G)-nitro L-arginine methyl ester) and L-NMMA (N(G)-monomethyl L-arginine) may enhance anesthesia indirectly by inhibiting the NO pathway. Moreover, NOS-I interact directly with receptor proteins. In an animal study, L-NMMA potentiated muscle relaxants. (2) The present experiments investigate the effects of L-NMMA, L-Name, and L-arginine on the nicotinic acetylcholine receptor channel (nAChR) using patch clamp techniques and a piezo-driven application system. Both NOS-I appear to directly interact with the nAChR in the open as well as in the closed conformation. L-Arginine has no effect.
Department of Anesthesiology, Technische Universität München, Klinikum rechts der Isar, Munich, Germany. hajo.schneck@lrz.tu-muenchen.de
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Scheller
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Blobner
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Von Loewenich
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Schneck
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Stadler
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Franke
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Kochs
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D008024:Ligands; D051379:Mice; D008870:Microtubules / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D008024:Ligands; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester