Nitric oxide modulation of Ca2+ responses in cow tracheal epithelium

Abstract

Nitric oxide (NO) plays an important role in the regulation of Ca²⁺-dependent airway epithelial function such as ciliary motility. In this experiment, the effect of NO on intracellular Ca²⁺ ([Ca²⁺]_i) was studied in cultured cow tracheal epithelium by the fura-2 method. $\text{L}\text{-N}{}^{\mathrm{<mtext>G</mtext>}}\text{-}\text{nitroarginine}$ methyl ester, an NO synthase inhibitor, per se did not significantly alter baseline [Ca²⁺]_i, but bradykinin- and ATP-induced increases in [Ca²⁺]_i were significantly reduced in the presence of $\text{L}\text{-N}{}^{\mathrm{<mtext>G</mtext>}}\text{-}\text{nitroarginine}$ methyl ester. This inhibitory effect disappeared by a simultaneous addition of L-arginine. Sodium nitroprusside or dibutyryl cyclic GMP potentiated bradykinin- and ATP-induced increases in [Ca²⁺]_i. Cytochemistry for NADPH diaphorase activity revealed the presence of NO synthase in the cultured epithelium. These results suggest that NO produced by NO synthase in airway epithelium modulates bradykinin- and ATP-induced [Ca²⁺]_i responses, which may be dependent on cyclic GMP.