title: Nitric oxide inhibits basolateral 10-pS Cl-channels through the cGMP/PKG signaling pathway in the thick ascending limb of C57BL/6 mice.
abstract: We used patch-clamp techniques to examine whether nitric oxide (NO) decreases NaCl reabsorption by suppressing basolateral 10-pS Cl-channels in the thick ascending limb (TAL). Both the NO synthase substrate l-arginine (l-Arg) and the NO donorS-nitroso-N-acetylpenicillamine significantly inhibited 10-pS Cl-channel activity in the TAL. The inhibitory effect of l-Arg on Cl-channels was completely abolished in the presence of the NO synthase inhibitor or NO scavenger. Moreover, inhibition of soluble guanylyl cyclase abrogated the effect of l-Arg on Cl-channels, whereas the cGMP analog 8-bromo-cGMP (8-BrcGMP) mimicked the effect of l-Arg and significantly decreased 10-pS Cl-channel activity, indicating that NO inhibits basolateral Cl-channels by increasing cGMP production. Furthermore, treatment of the TAL with a PKG inhibitor blocked the effect of l-Arg and 8-BrcGMP on Cl-channels, respectively. In contrast, a phosphodiesterase 2 inhibitor had no significant effect on l-Arg or 8-BrcGMP-induced inhibition of Cl-channels. Therefore, we conclude that NO decreases basolateral 10-pS Cl-channel activity through a cGMP-dependent PKG pathway, which may contribute to the natriuretic and diuretic effects of NO in vivo.
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, China.
authors.forename: Zhongxiuzi
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, China.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, China qizhi@xmu.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D018118:Chloride Channels / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D008138:Loop of Henle / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D018118:Chloride Channels; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP
keywords: Cl− channel; cGMP; nitric oxide; protein kinase G; thick ascending limb