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dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through thecGMP/cGMP-dependent protein kinase pathway

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World Journal of Gastroenterology 2008年第35期14卷 5461-5466页

作者： Chun-Yu Cai Zheng-Xu Cai Xin-Yi Gu Lu-Juan Shan Yong-Xiao Wang Xue-Zhe Yin Qing-Hui Qi Hui-Shu Guo Department of Internal Medicine the Affiliated Hospital of Yanbian University Yanji 133000 Jilin Province China Department of Neurology the First Affiliated Hospital of Dalian Medical University Dalian 116011 Liaoning Province China Centralab Zhongshan Affiliated Hospital of Dalian University Dalian 116001 Liaoning Province China Centralab the First Affiliated Hospital of Dalian Medical University Dalian 116011 Liaoning Province China Center for Cardiovascular Sciences Albany Medical College Albany NY 12208 United States

AIM: 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 Ca2+-activated K+ currents (IK(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 gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(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. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway.

关键词： dendroaspis natriuretic peptide Cyclic guanosine monophosphate Protein kinase G Proteinkinase A Gastric motility

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Inhibitory effect of dendroaspis natriuretic peptide on spontaneous contraction in gastric antral circular smooth muscles of guinea pigs

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Acta Pharmacologica Sinica 2007年第11期28卷 1797-1802页

作者： Hui-shu GUO~(2,5),Zheng-xu CAI~3,Tai-hua WU~2,Jing XU~3,Yang QIU~2,Wen-xie XU~4~2 Centralab and ~3 Department of Neurology,The Fist Affiliated Hospital of Dalian Medical University,Dalian 116011,China ~4 Department ofPhysiology Shanghai Jiao Tong University Medical College,Shanghai 200240,China Centralab The Fist Affiliated Hospital of Dalian Medical University Dalian China Department of Neurology The Fist Affiliated Hospital of Dalian Medical University Dalian China Department of Physiology Shanghai Jiao Tong University Medical College Shanghai China

Aim:To determine whether the natriuretic peptide receptor (NPR) is present in thestomach of guinea pigs and to investigate the effect of dendroaspis natriureticpeptide (DNP) on the gastric motility of guinea pigs and its ***:The distribution of the NPR was analyzed by *** spon-taneous contraction of gastric antral circular muscles of guinea pigs was recordedby a 4-channel *** whole cell patch-clamp technique was intro-duced to record calcium-activated potassium currents in the gastric myocytesisolated by ***:The NPR existed in the gastric fundus,gastricbody,and gastric antrum of guinea pigs,and its density was largest in the *** inhibited spontaneous contraction and exhibited a *** DNP-induced inhibition was diminished by LY83583 (a guanylatecyclase inhibitor) and was potentiated by zaprinast (a cGMP-sensitivephosphoesterase inhibitor).The inhibitory effect of DNP on spontaneous con-traction was also inhibited by tetraethylammonium (a non-selective potassiumchannel blocker);10 nmol/L DNP increased the calcium-activated potassium cur-rents in the gastric circular myocytes of guinea ***:The NPR ismost common in the gastric antrum of guinea *** significantly inhibitsgastric motility in the gastric antrum of guinea *** inhibitory effect occursvia a cGMP-dependent pathway,and a calcium-activated potassium channel maybe also involved in the relaxation induced by DNP in gastric antral circular smoothmuscles.

关键词： dendroaspis natriuretic peptide motility natriuretic peptide receptor spontaneous contraction

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