Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through the cGMP/cGMP-dependent protein kinase pathway.
OBJECTIVE
To systematically investigate if cGMP/cGMP-dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle.


METHODS
The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca(2+)-activated K(+) currents (I(K(Ca))) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique.


RESULTS
DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastric antral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased I(K(Ca)). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor.


CONCLUSIONS
DNP activates I(K(Ca)) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/PKA pathway.
Cai
Chun-Yu
CY
Centralab, the first Affiliated Hospital of Dalian Medical Universty and Zhongshan Affiliated Hospital of Dalian University, Dalian 116011, Liaoning Province, China.
Cai
Zheng-Xu
ZX
Gu
Xin-Yi
XY
Shan
Lu-Juan
LJ
Wang
Yong-Xiao
YX
Yin
Xue-Zhe
XZ
Qi
Qing-Hui
QH
Guo
Hui-Shu
HS
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D006152:Cyclic GMP / Q000096:biosynthesis; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D004546:Elapid Venoms / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D002227:Carbazoles; C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C073601:KT 5823; C057416:KT 5720; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP