HS-142-1,a Novel Non-peptide Antagonist for Atrial Natriuretic Peptide Receptor, Selectively Inhibits Particulate Guanylyl Cyclase and Lowers Cyclic GMP in LLC-PK_1 Cells

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概要

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• HS-142-1,a novel atrial natriuretic peptide (ANP) antagonist isolated from the culture broth of Aureobasidium sp., selectively inhibits ANP-induced cyclic GMP accumulation in porcine kidney epithelial LLC-PK_1 cells. At concentrations from 0.1 to 100 μg/ml (=2.5×10^<-8>-2.5×10^<-5>M, given the mean molecular weight is 4,000), HS-142-1 prevents intracellular cyclic GMP accumulation initiated by 10^<-8>M rat ANP in a dose-dependent manner, but not cyclic GMP accumulation produced by 10^<-5>M sodium nitroprusside. HS-142-1 alone has no effects on the basal level of cyclic GMP seen in the absence of ANP. No change of intracellular cyclic AMP was observed upon the treatment of the cells with HS-142-1. Further, the selectivity of HS-142-1 for the guanylyl cyclase-linked receptor was confirmed by affinity labeling studies with bovine adrenocortical membranes. HS-142-1 specifically abolished the labeling of the guanylyl cyclase-linked 135-kDa band in a dose-dependent manner, but not the labeling of the 60-kDa band not coupled to the guanylyl cyclase. These results show that HS-142-1 selectively inhibits ANP-mediated accumulatiion of cyclic GMP in LLC-PK_1 cells through interacting with guanylyl cyclase-linked receptors.

• 社団法人日本農芸化学会の論文
• 1992-07-23

著者

• Yoshida M

  National Agricultural Research Center For Hokkaido Region

• NAKAJO Shigeo

  Laboratory of Biochemistry, Yokohama College of Pharmacy

• MATSUDA YUZURU

  Tokyo Research Laboratories, kyowa Hakko Kogyo Co., Ltd

• TANAKA Takeo

  Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.

• Inagami Tadashi

  Department of Biochemistry, Vanderbilt University School of Medicine

• Inagami Tadashi

  Department Of Biochemistry And Hypertension Center School Of Medicine Vanderbilt University

• MORISHITA Yoshikazu

  Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.

• Matsuda Yuzuru

  President Kyowa Hakko Kogyo Co. Ltd.

• Matsuda Yuzuru

  Tokyo Research Laboratories Kyowa Hakko Kogyo Co. Ltd.

• Tanaka Takeo

  Tokyo Research Laboratories Kyowa Hakko Kogyo Co. Ltd.

• NAKAJO Shigeo

  Department of Anatomy, School of Medicine, Showa University

• Ichimura Michio

  Department Of Biochemistry Vanderbilt University School Of Medicine

• Toki S

  Department Of Biofunctional Chemistry Faculty Of Agriculture Kobe University

• Nakajo S

  Laboratory Of Biochemistry Yokohama College Of Pharmacy

• Sano Taketo

  Department of Applied Biological Chemistry, Faculty of Agriculture, Tohoku University

• SNAJDAR Rudolf

  Department of Biochemistry, Vanderbilt University, School of Medicine

• SANO Tomoyuki

  Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.

• YAMADA Koji

  Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.

• Snajdar Rudolf

  Department Of Biochemistry Vanderbilt University School Of Medicine

• Sano Taketo

  Department Of Applied Biological Chemistry Faculty Of Agriculture Tohoku University

• Yamada Koji

  Pharmaceutical Research Laboratories Kyowa Hakko Kogyo Co. Ltd.

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