Inhibitory Effect of Several Nitric Oxide‐Generating Compounds on Purified Na⁺,K⁺‐ATPase Activity from Porcine Cerebral Cortex

Abstract

Nitric oxide (NO)-generating compounds (NO donors) such as sodium nitroprusside, S-nitroso-N-acetylpenicillamine, S-nitroso-L-glutathione, 3-morpholinosydnonimine (SIN-i), (DL)-(E)-ethyl-2-[(E)-hydroxyimino] -5-nitro-3-hexenamide, and i -hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-i -triazene inhibited the Na~,K~-ATPase activity purified from porcine cerebral cortex. NO-reducing or -scavenging agents, such as superoxide dismutase or N-(dithiocarbamate)-Nmethyl-D-glucamine sodium salt, L-ascorbic acid, and sulfhydryl (SH) compounds, such as dithiothreitol or the reduced form of glutathione, but not a-tocopherol, prevented the inhibition of the enzyme activity by all NO donors except sodium nitroprusside. Enzyme inhibition could also be reversed by these SH compounds, but not by superoxide dismutase, L-ascorbic acid, and a-tocopherol. 2 -(4-Carboxyphenyl)-4, 4,5, 5-tetramethylimidazolin-i-oxyl 3-oxide (PTIO), which is able to scavenge NO radicals and generate nitrogen dioxide radicals (NO 2), potentiated the inhibition of this enzyme activity induced by all NO donors (except SIN-i). PTIO did not potentiate, but rather attenuated, the SIN-i -induced inhibition. SIN-i has been reported to release both NO and superoxide and thereby to rapidly form peroxynitrite (ONOO). These potentiated and attenuated inhibitions of the enzyme activity induced by PTIO plus all of the NO donors except sodium nitroprusside were prevented by SH compounds, but not by superoxide dismutase, Lascorbic acid, and es-tocopherol. These results suggest that NO donors may release NO or NO-derived products, presumably N02 and ONOO, and may inhibit the Na~,K~-ATPase activity by interacting with a SH group at the active site of the enzyme.

Regulation of Na+/K+-ATPase activity by nitric oxide in the kidney and gill of the brown trout (Salmo trutta)

“…Activation of the sGC leads to increased intracellular cGMP concentrations and is believed to mediate many of the physiological effects of NO, even though cGMP-independent effects have also been described (Gupta et al, 1994;Sato et al, 1997). The present study demonstrated increased wholetissue cGMP concentration in response to SNP, apparently by activating sGC in both tissues.…”

“…Nitric oxide has been shown to modulate ion transport in several mammalian tissues, the effect apparently being tissue dependent. Inhibitory effects on the Na + /K + -ATPase have been found in the kidney (opossum, Liang and Knox, 1999;rat, McKee et al, 1994), the choroid plexus (bovine, Ellis et al, 2000), alveolar cells (rat, Guo et al, 1998), aortic endothelial cells (porcine, Gruwel and Williams, 1998), liver (rat, Muriel and Sandoval, 2000) and brain (porcine, Sato et al, 1997). Stimulatory effects have been found in rat trachea (de Oliveira Elias et al, 1999) and rabbit aorta (Gupta et al, 1994).…”

Nitric Oxide Increases the Expression of Aquaporin-4 Protein in Rat Optic Nerve Astrocytes through the Cyclic Guanosine Monophosphate/Protein Kinase G Pathway

“…In addition, the SNAP-induced increase in cellular volume was observed under isosmotic conditions. Although the exact mechanism was not determined, NO is known to inhibit Na + /K + -ATPase [45,46]. This inhibition may cause an increase in intracellular sodium, leading to water influx through AQP4 [47].…”

Spatiotemporal Patterns of Dexamethasone-Induced Ras Protein 1 Expression in the Central Nervous System of Rats with Experimental Autoimmune Encephalomyelitis

“…Glycogen phosphorylase activity is stimulated by NO, which would increase tissue levels of glucose-1-phosphate and deplete cellular glycogen (Borgs et al 1996). S-nitrosylation of the sodium pump, which inhibits its activity, may account for membrane depolarization associated with NO-mediated cell death (Sato et al 1997). But how might neural NO gain access to its targets in the presence of millimolar concentrations of glutathione, which would likely sequester freely diffusing cytosolic NO?…”