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

被引:28
作者
Duszyk, M [1 ]
机构
[1] Univ Alberta, Dept Physiol, Edmonton, AB T6G 2H7, Canada
关键词
Calu-3; cells; guanosine 3 ' 5 '-cyclic monophosphate; chloride channels; potassium channels;
D O I
10.1152/ajplung.2001.281.2.L450
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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, N-G-nitro-L-arginine methyl ester, reduced short-circuit current (Isc), whereas an NO donor, S-nitrosoglutathione (GSNO), increased I-sc, with an EC50 similar to1.2 muM. 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-alpha ]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).
引用
收藏
页码:L450 / L457
页数:8
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