Dynamics of nitric oxide during simulated ischaemia-reperfusion in rat striatal slices measured using an intrinsic biosensor, soluble guanylyl cyclase

The European Journal of Neuroscience
Charmaine GriffithsJ Garthwaite

Abstract

Nitric oxide (NO) may act as a toxin in several neuropathologies, including the brain damage resulting from cerebral ischaemia. Rat striatal slices were used to determine the mechanism of enhanced NO release following simulated ischaemia and, for estimating the NO concentrations, the activity of guanylyl cyclase served as a biosensor. Exposure of the slices for 10 min to an oxygen- and glucose-free medium caused a 70% fall in cGMP levels. On recovery, cGMP increased 2-fold above basal, where it remained for 40 min before declining. The pattern of changes matched those of cGMP or NO oxidation products measured during and after brain ischaemia in vivo. The increase observed during the recovery period was blocked by inhibition of NO synthase or NMDA receptors and was curtailed by tetrodotoxin, implying that it was caused by glutamate release leading to activation of the NMDA receptor-NO synthase pathway. Calibration of the cGMP levels against NO-stimulated guanylyl cyclase yielded a basal NO concentration of 0.6 nm. The peak NO concentration achieved on recovery from simulated ischaemia was estimated as 0.8 nm. These values are compatible with the low micromolar concentrations of NO oxidation products (chiefly nitrate) found by mi...Continue Reading

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Citations

Mar 31, 2004·Molecular Aspects of Medicine·Ana LedoJoão Laranjinha
Oct 3, 2002·Journal of Neurochemistry·Victoria WykesJohn Garthwaite
Oct 22, 2011·The Journal of Biological Chemistry·Katherine C WoodJohn Garthwaite
Sep 9, 2006·Neuroscience Letters·Natalia B Saulskaya, Nellia V Fofonova
Mar 16, 2004·The European Journal of Neuroscience·Robert G KeynesJohn Garthwaite
Apr 14, 2004·The European Journal of Neuroscience·Rachel HopperJohn Garthwaite
Jul 1, 2008·The European Journal of Neuroscience·John Garthwaite
Aug 25, 2009·Brain Research·Santina ZanelliJaideep Kapur
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May 25, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sheng WangSergey Kasparov

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