title: Regulation of anion secretion by nitric oxide in human airway epithelial cells.
abstract: Nitric oxide (NO) is continuously produced and released in human airways, but the biological significance of this process is unknown. In this study, we have used Calu-3 cells to investigate the effects of NO on transepithelial anion secretion. An inhibitor of NO synthase, NG-nitro-L-arginine methyl ester, reduced short- circuit current (I(sc)), whereas an NO donor, S-nitrosoglutathione (GSNO), increased I(sc), with an EC50 approximately 1.2 microM. The NO-activated current was inhibited by diphenylamine-2-carboxylate, clotrimazole, and charybdotoxin. Selective permeabilization of cell membranes indicated that NO activated both apical anion channels and basolateral potassium channels. An inhibitor of soluble guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, prevented activation of I(sc) by NO but not by 8-bromo-cGMP, suggesting that NO acts via a cGMP-dependent pathway. Sequential treatment of cells with forskolin and GSNO or 1-ethyl-2-benzimidazolinone and GSNO showed additive effects of these chemicals on I(sc). Interestingly, GSNO elevated intracellular Ca2+ concentration ([Ca2+]i) but had no effect on I(sc) activated by thapsigargin. These results show that NO activates transepithelial anion secretion via a cGMP-dependent pathway that involves cross talk between NO and [Ca2+]i.
authors: Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada. marek.duszyk@ualberta.ca
authors: M
authors: M
authors: Duszyk
mesh_terms: D000838:Anions / Q000378:metabolism*; D001562:Benzimidazoles / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects / Q000502:physiology; D004553:Electric Conductivity; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D026422:S-Nitrosoglutathione
chemical_list: D000838:Anions; D001562:Benzimidazoles; C505032:CFTR protein, human; D002120:Calcium Channel Agonists; D007473:Ion Channels; D009603:Nitroso Compounds; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D019001:Nitric Oxide Synthase; D005978:Glutathione; D006152:Cyclic GMP; C102635:1-ethyl-2-benzimidazolinone