Effects of Dendroaspis natriuretic peptide on delayed rectifier potassium currents and its mechanism.
Dendroaspis natriuretic peptide (DNP), a newly-described natriuretic peptide, plays an inhibitory role in smooth muscle motility of the gastrointestinal tract. However, the effect of DNP on delayed rectifier potassium currents I(K(V)) is still unclear. In this study, we sought to investigate the effect of DNP on I(K(V)) and its mechanism in gastric antral circular smooth muscle cells using the whole-cell patch-clamp technique. DNP significantly inhibited I(K(V)) in a concentration-dependent manner. LY83583 (1 micromol/l), a guanylate cyclase inhibitor, significantly impaired DNP-induced inhibition of I(K(V)). Moreover, DNP-induced inhibition in I(K(V)) was potentiated by the cyclic guanosine monophosphate (cGMP) sensitive phosphoesterase inhibitor zaparinast (0.1 micromol/l). DNP-induced inhibition of I(K(V)) was completely blocked by KT5823, an inhibitor of cGMP-dependent protein kinase G(PKG), but not affected by KT-5720, a PKA-specific inhibitor. Taken together, our results suggest that DNP inhibits I(K(V)) via the cGMP/PKG-dependent signaling axis instead of the cAMP/PKA pathway.
Gu
Xin-Yi
XY
Department of internal medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China.
Cai
Zheng-Xu
ZX
Yuan
Hong
H
Wu
Tai-Hua
TH
Li
Jian
J
Guo
Hui-Shu
HS
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004546:Elapid Venoms / Q000494:pharmacology*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D000634:Aminoquinolines; D002227:Carbazoles; C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D011758:Pyrroles; C073601:KT 5823; C057416:KT 5720; C041715:6-anilino-5,8-quinolinedione; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP