Intercellular action of nitric oxide in adult rat cerebellar slices.
Nitric oxide (NO) is a novel messenger molecule that is produced following glutamate receptor activation and which stimulates cyclic GMP (cGMP) formation. To determine if the mode of action of NO is predominantly intra- or inter-cellular in intact brain tissue, we tested the ability of haemoglobin (Hb), a NO-binding protein that remains extracellular, to inhibit cGMP accumulation induced by glutamate receptor agonists in adult rat cerebellar slices. Responses to agonists acting selectively on N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors were inhibited by Hb (IC50 approximately 20 microM) suggesting that NO functions predominantly as a mediator of communication between cells. The effects of NO-donating drugs (e.g. nitroprusside) were also inhibited by Hb, implying that they yield NO extracellularly.
Department of Physiology, University of Liverpool, UK.
E
E
Southam
J
J
Garthwaite
D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism; D004347:Drug Interactions; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006454:Hemoglobins / Q000494:pharmacology; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000494:pharmacology; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D006454:Hemoglobins; D006898:Hydroxylamines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D009599:Nitroprusside; D007051:Ibotenic Acid; D019811:Hydroxylamine; D009569:Nitric Oxide; D018698:Glutamic Acid; C002385:linsidomine; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D010396:Penicillamine; D006152:Cyclic GMP; D007608:Kainic Acid