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

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 

机构地区：[1]Department of Internal Medicine, the Affiliated Hospital of Yanbian University, Yanji 133000, Jilin Province, China [2]Department of Neurology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China [3]Centralab, Zhongshan Affiliated Hospital of Dalian University, Dalian 116001, Liaoning Province, China [4]Centralab, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China [5]Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States

出　　处：《World Journal of Gastroenterology》2008年第35期5461-5466,共6页世界胃肠病学杂志（英文版）

基　　金：The National Natural Science Foundation of China, No. 30800382;the Youth Science Foundation of Dalian to Professor Hui-Shu Guo, No. 2006B3NS218

摘　　要：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.AIM： To systematically investigate if cGMP/cGMPdependent 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 （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 gastric antral 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 

分 类 号：R333.2[医药卫生—人体生理学]