Details

Autor(en) / Beteiligte

• Tanaka, T. (Kyowa Hakko Kogyo Co. Ltd., Machida, Tokyo (Japan). Tokyo Research Lab.)
• Ichimura, M
• Nakajo, S
• Snajdar, R.M
• Morishita, Y
• Sano, T
• Yamada, K
• Inagami, T
• Matsuda, Y

Titel

HS-142-1, a novel non-peptide antagonist for atrial natriuretic peptide receptor, selectively inhibits particulate guanylyl cyclase and lowers cyclic GMP in LLC-PK1 cells

Ist Teil von

• Bioscience, biotechnology, and biochemistry, 1992, Vol.56 (7), p.1041-1045

Ort / Verlag

Tokyo: Taylor & Francis

Erscheinungsjahr

1992

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 accumulation of cyclic GMP in LLC-PK 1 cells through interacting with guanylyl cyclase-linked receptors.