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

Abstract

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.