title: Different nitric oxide synthase inhibitors cause rapid and differential alterations in the ligand-binding capacity of transmitter receptors in the rat cerebral cortex.
abstract: Inhibitors of nitric oxide (NO) synthesis reduce postlesional neuronal death during reperfusion injury by reducing the NO-mediated increase in excitatory neurotransmitter-release. The protective effects of various NO-synthase (NOS) inhibitors differ due to their isoform selectivity. The effects of NO-mediated excessive neurotransmitter supply are transmitted via specific neurotransmitter receptors expressed by the target cells. We report changes in the ligand-binding of different excitatory and inhibitory neurotransmitter-receptors studied by in vitro receptor autoradiography after in vivo-application of NOS-inhibitors. Since the constitutively expressed neuronal NOS-I is area-specifically distributed within the rat cortex, numerous cortical areas were studied in non-lesioned rats, in order to analyze the area-specific effects of NOS-inhibitors. The results showed that the NOS-I-specific inhibitor 7-nitroindazole increased binding of 3H-muscimol, 3H-pirenzepine and 3H-kainate, whereas the less isoform-specific, general NOS-inhibitor L-nitroarginine increased binding of 3H-muscimol and 3H-AMPA in most cortical areas, leaving 3H-kainate binding almost unchanged. The water soluble L-nitroarginine-methylester caused similar effects to those of L-nitroarginine which changed over a period of chronic treatment. The inhibitory GABAA-receptors were increased after NOS-inhibition in most cortical areas, whereas binding of 3H-Oxotremorine-M (acetylcholine receptors), 3H-MK-801 (NMDA-receptors) and 3H-AMPA (AMPA receptors) was affected differently among the cortical areas. Strongest alterations of ligand-binding capacity after administration of NOS-inhibitors were seen in cortical areas known to contain the highest packing densities of NOS-I-positive interneurons such as the piriform and entorhinal cortices, indicating that, in normal animals, neurotransmission and probably cognitive information processing would be affected by the pharmacological modulation of nitric oxide production.
authors.affiliation: Institute für Neuroanatomie und Hirnforschung, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Bidmon
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: N
authors.initials: N
authors.lastname: Palomero-Gallagher
authors.forename: E
authors.initials: E
authors.lastname: Oermann
authors.forename: B
authors.initials: B
authors.lastname: Mayer
authors.forename: A
authors.initials: A
authors.lastname: Schleicher
authors.forename: K
authors.initials: K
authors.lastname: Zilles
mesh_terms: D000818:Animals; D001345:Autoradiography; D002540:Cerebral Cortex / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D010095:Oxotremorine / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D016291:Dizocilpine Maleate; D007608:Kainic Acid; D009118:Muscimol; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010095:Oxotremorine; D018091:Receptors, AMPA; D011950:Receptors, Cholinergic; D011963:Receptors, GABA-A; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid