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 (Isc). This effect was significantly reduced by the NO synthase inhibitor NG-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 Isc increased. The SNAP-induced decrease in 86Rb 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 x 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.
Aizman
R
R
Department of Woman and Child Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, S-17176 Stockholm, Sweden.
Brismar
H
H
Celsi
G
G
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D003106:Colon / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010069:Oxadiazoles / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D006162:Guanylate Cyclase; D010396:Penicillamine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester