Inhibitory effect of S-nitroso-N-acetylpenicillamine on the basolateral 10-pS Cl.sup.- channel in thick ascending limb

We have previously reported that L-arginine, a nitric oxide synthase substrate, inhibits the basolateral 10-pS Cl.sup.- channel through the cGMP/PKG signaling pathway in the thick ascending limb (TAL). As a NO releasing agent, the effect of S-nitroso-N-acetyl-penicillamine (SNAP) on the channel acti...

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Veröffentlicht in:PloS one 2023-04, Vol.18 (4), p.e0284707
Hauptverfasser: Ye, Shiwei, Wu, Peng, Gao, Zhongxiuzi, Wang, Mingyan, Zhou, Li, Qi, Zhi
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Sprache:eng
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Zusammenfassung:We have previously reported that L-arginine, a nitric oxide synthase substrate, inhibits the basolateral 10-pS Cl.sup.- channel through the cGMP/PKG signaling pathway in the thick ascending limb (TAL). As a NO releasing agent, the effect of S-nitroso-N-acetyl-penicillamine (SNAP) on the channel activity was examined in thick ascending limb of C57BL/6 mice in the present study. SNAP inhibited the basolateral 10-pS Cl.sup.- channel in a dose-dependent manner with an IC50 value of 6.6 [mu]M. The inhibitory effect of SNAP was abolished not only by NO scavenger (carboxy-PTIO) but also by blockers of soluble guanylate cyclase (ODQ or LY-83583), indicating that the cGMP-dependent signaling pathway is involved. Moreover, the inhibitory effect of SNAP on the channel was strongly attenuated by a protein kinase G (PKG)-specific inhibitor, KT-5823, but not by the PDE2 inhibitor, BAY-60-7550. We concluded that SNAP inhibited the basolateral 10-pS Cl.sup.- channels in the TAL through a cGMP/PKG signaling pathway. As the 10-pS Cl.sup.- channel is important for regulation of NaCl absorption along the nephron, these data suggest that SNAP might be served as a regulator to prevent high-salt absorption related diseases, such as hypertension.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0284707