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World J Gastroenterol. Sep 21, 2008; 14(35): 5461-5466
Published online Sep 21, 2008. doi: 10.3748/wjg.14.5461
Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through the cGMP/cGMP-dependent protein kinase pathway
Chun-Yu Cai, Zheng-Xu Cai, Xin-Yi Gu, Lu-Juan Shan, Yong-Xiao Wang, Xue-Zhe Yin, Qing-Hui Qi, Hui-Shu Guo
Chun-Yu Cai, Hui-Shu Guo, Lu-Juan Shan, Qing-Hui Qi, Centralab, the first Affiliated Hospital of Dalian Medical Universty, Dalian 116011, Liaoning Province, China
Chun-Yu Cai, Xue-Zhe Yin, Department of internal medicine, the first Affiliated Hospital of Yanbian University College of Medicine, Yanji 133000, Jilin Province, China
Zheng-Xu Cai, Department of Neurology, the first Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
Hui-Shu Guo, Xin-Yi Gu, Centralab, Zhongshan Affiliated Hospital of Dalian University, Dalian 116001, Liaoning Province, China
Yong-Xiao Wang, Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, United States
Author contributions: Guo HS and Qi QH designed research; Cai CY, Cai ZX, Gu XY and Shan LJ performed research; Yin XZ contributed new analytic tools; Cai CY and Cai ZX analyzed data; Wang YX corrected syntax; Cai CY, Cai ZX and Guo HS wrote the paper.
Supported by The National Natural Science Foundation of China, No. 30800382 and the Youth Science Foundation of Dalian to Professor Hui-Shu Guo, No. 2006B3NS218
Correspondence to: Hui-Shu Guo, Professor, Centralab, the first Affiliated Hospital of Dalian Medical Universty and Zhongshan Affiliated Hospital of Dalian University, Dalian 116011, Liaoning Province, China. guohuishu1@msn.com
Telephone: +86-411-83635963-2237 Fax: +86-411-83622844
Received: April 18, 2008
Revised: August 22, 2008
Accepted: August 29, 2008
Published online: September 21, 2008
Abstract

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 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.

Keywords: Dendroaspis natriuretic peptide, Cyclic guanosine monophosphate, Protein kinase G, Protein kinase A, Gastric motility