HS-142-1, A NOVEL NONPEPTIDE ANTAGONIST FOR ATRIAL-NATRIURETIC-PEPTIDE RECEPTOR, SELECTIVELY INHIBITS PARTICULATE GUANYLYL CYCLASE AND LOWERS CYCLIC-GMP IN LLC-PK1 CELLS

被引:16
作者
TANAKA, T
ICHIMURA, M
NAKAJO, S
SNAJDAR, RM
MORISHITA, Y
SANO, T
YAMADA, K
INAGAMI, T
MATSUDA, Y
机构
[1] KYOWA HAKKO KOGYO CO LTD, TOKYO RES LABS, 3-3-6 ASAHI MACHI, MACHIDA, TOKYO 194, JAPAN
[2] KYOWA HAKKO KOGYO CO LTD, PHARMACEUT RES LABS, NAGAIZUMI, SHIZUOKA 411, JAPAN
[3] VANDERBILT UNIV, MED CTR, SCH MED, DEPT BIOCHEM, NASHVILLE, TN 37232 USA
关键词
D O I
10.1271/bbb.56.1041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-PK1 cells. At concentrations from 0.1 to 100-mu-g/ml (= 2.5 x 10(-8) - 2.5 x 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-PK1 cells through interacting with guanylyl cyclase-linked receptors.
引用
收藏
页码:1041 / 1045
页数:5
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