Nitric oxide modulates Na⁺, K⁺-ATPase activity through cyclic GMP pathway in proximal rat trachea

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• 作者：de Oliveira Elias ; Miriam ; de Lima ; Wothan Tavares ; Vannuchi ; Yuri Borges ; Marcourakis ; Tania ; et. al.
• 关键词：Nitric oxide (NO) ; cGMP ; Protein kinase G ; Na⁺ ; K⁺-ATPase ; Trachea ; rat
• 刊名：European Journal of Pharmacology
• 出版年：1999
• 出版时间：February 19, 1999
• 年：1999
• 卷：367
• 期：2-3
• 页码：307-314
• 全文大小：374 K

文摘

The present work demonstrated that nitric oxide (NO) modulates Na⁺, K⁺-ATPase activity in the proximal rat trachea. Sodium nitroprusside induced concentration-dependent (10–100 μM) stimulation in proximal trachea Na⁺, K⁺-ATPase activity. The effect was specific for Na⁺, K⁺-ATPase since Mg-ATPase activity was unaffected. This NO-donor changed neither Na⁺, K⁺-ATPase nor Mg-ATPase activity in the distal segment. The modulatory action on Na⁺, K⁺-ATPase induced by sodium nitroprusside was linked to an increase in nitrates/nitrites and cyclic GMP levels in proximal segments. Modulation of proximal Na⁺, K⁺-ATPase activity by sodium nitroprusside was mimicked by S-nitroso-N-acetylpenicillamine (100 μM) and 8-bromo-cyclic GMP (100 μM). Both sodium nitroprusside and 8-bromo-cyclic GMP effects on Na⁺, K⁺-ATPase activity of proximal segments of trachea were blocked by 2 μM of KT 5823 (a cyclic GMP-dependent protein kinase inhibitor), but not by 0.5 μM of KT 5720 (a cyclic AMP-dependent protein kinase inhibitor). Both kinase inhibitors decreased proximal Na⁺, K⁺-ATPase activity, but did not change Mg-ATPase activity. Okadaic acid (1 μM), a phosphatase-1 inhibitor, increased proximal Na⁺, K⁺-ATPase but not Mg-ATPase activity. The effect of okadaic acid was non-additive with that of 8-bromo-cGMP on Na⁺, K⁺-ATPase activity. Our results suggest that NO modulates proximal rat trachea Na⁺, K⁺-ATPase activity through cyclic GMP and cyclic GMP-dependent protein kinase.