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

The present work demonstrated that nitric oxide (NO) modulates Na+, K+-ATPa se activity in the proximal rat trachea. Sodium nitroprusside induced conce ntration-dependent (10-100 mu M) stimulation in proximal trachea Na+, K+-AT Pase activity. The effect was specific for Na+, K+-ATPase since Mg-ATPase a ctivity was unaffected. This NO-donor changed neither Na+, K+-ATPase nor Mg -ATPase activity in the distal segment. The modulatory action on Na+, K+-AT Pase 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 mu M) and 8-bromo-cyclic GMP (100 mu M). Both so dium nitroprusside and 8-bromo-cyclic GMP effects on Na+, K+-ATPase activit y of proximal segments of trachea were blocked by 2 mu M of KT 5823 (a cycl ic GMP-dependent protein kinase inhibitor), but not by 0.5 mu M of KT 5720 (a cyclic AMP-dependent protein kinase inhibitor). Both kinase inhibitors d ecreased proximal Na+, K+-ATPase activity, but did not change Mg-ATPase act ivity. Okadaic acid (1 mu M), 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 resu lts suggest that NO modulates proximal rat trachea Na+, K+-ATPase activity through cyclic GMP and cyclic GMP-dependent protein kinase. (C) 1999 Elsevi er Science B.V. All rights reserved.