Regulation of anion secretion by nitric oxide in human airway epithelial cells

Am J Physiol Lung Cell Mol Physiol. 2001 Aug;281(2):L450-7. doi: 10.1152/ajplung.2001.281.2.L450.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anions / metabolism*
  • Benzimidazoles / pharmacology
  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / metabolism*
  • Calcium Channel Agonists / pharmacology
  • Cell Line
  • Colforsin / pharmacology
  • Cyclic GMP / physiology
  • Cystic Fibrosis Transmembrane Conductance Regulator / drug effects
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology
  • Electric Conductivity
  • Glutathione / analogs & derivatives*
  • Glutathione / pharmacology
  • Humans
  • Ion Channels / drug effects
  • Ion Channels / physiology
  • Nitric Oxide / pharmacology
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / metabolism
  • Nitroso Compounds / pharmacology
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism*
  • S-Nitrosoglutathione


  • Anions
  • Benzimidazoles
  • CFTR protein, human
  • Calcium Channel Agonists
  • Ion Channels
  • Nitroso Compounds
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Colforsin
  • Nitric Oxide
  • S-Nitrosoglutathione
  • Nitric Oxide Synthase
  • Glutathione
  • Cyclic GMP
  • 1-ethyl-2-benzimidazolinone