Nitric oxide inhibits potassium transport in the rat distal colon.

The effect of the nitric oxide (NO) pathway on K+ (measured using 86Rb) transport in adult rat distal colon was investigated in muscle-stripped segments of colons mounted in Ussing chambers. When added to the mucosal solution, the endogenous precursor of NO, l-arginine (30 mM), inhibited both mucosal-to-serosal and serosal-to-mucosal 86Rb fluxes and caused a prolonged decrease of short-circuit current ( I sc). This effect was significantly reduced by the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) but not by d-NAME. Mucosal application of S-nitroso- N-acetyl-penicillamine (SNAP) inhibited mucosal-to-serosal 86Rb flux without affecting serosal-to-mucosal transport. Serosal addition of two different exogenous NO donors, sodium nitroprusside (0.1 mM) and SNAP (0.2 mM), decreased serosal-to-mucosal 86Rb flux, whereas I sc increased. The SNAP-induced decrease in86Rb flux was abolished by 1H-(1,2,4)oxodiazolo(4,3-a)quinoxalin-1-one (0.2 mM), a selective inhibitor of NO-stimulated soluble guanylyl cyclase, and by methylene blue (0.01 mM). Addition of 8-bromo-cGMP (2 × 10-4 M) in the presence of an inhibitor of cGMP-specific phosphodiesterase mimicked the effects of NO-donating compounds. This study provides evidence that NO inhibits K+ transport in the rat distal colon via a cGMP-dependent pathway. The effect on net K+transport may depend on the side of NO action.