CELLULAR MECHANISMS FOR SYNTHESIS AND SECRETION OF ATRIAL-NATRIURETIC-PEPTIDE AND BRAIN NATRIURETIC PEPTIDE IN CULTURED RAT ATRIAL CELLS

被引:86
作者
SUZUKI, E
HIRATA, Y
KOHMOTO, O
SUGIMOTO, T
HAYAKAWA, H
MATSUOKA, H
SUGIMOTO, T
KOJIMA, M
KANGAWA, K
MINAMINO, N
MATSUO, H
机构
[1] UNIV TOKYO,FAC MED,DEPT INTERNAL MED 2,7-3-1 HONGO,BUNKYO KU,TOKYO 113,JAPAN
[2] MIYAZAKI MED COLL,DEPT BIOCHEM 2,MIYAZAKI 88916,JAPAN
[3] NATL CARDIOVASC CTR,RES INST,SUITA,OSAKA 565,JAPAN
关键词
CALCIUM; PROTEIN KINASE-C; ENDOTHELIN; MESSENGER-RNA;
D O I
10.1161/01.RES.71.5.1039
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To investigate the cellular mechanism for the synthesis and secretion of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), we examined the effects of vasoactive agents on the secretion rates and gene expression of ANP and BNP in cultured rat atrial cells. Endothelin (10(-7) M, +61%), 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-6) M, +62%), the calcium ionophore A23187 (10(-6) M, +95%), and Bay K 8644 (10(-6) M, +34%) (p<0.05 each) all increased the secretion of ANP into the culture media in a dose-dependent fashion. On the other hand, endothelin (10(-7) M, +57%) and TPA (10(-6) M, +55%) (p<0.01 each) increased the secretion of BNP in a dose-dependent manner, whereas A23187 (10(-6) M, -45%, p<0.001) suppressed the secretion of BNP in a dose-dependent manner, and Bay K 8644 caused no significant effects on BNP secretion. The molecular forms of intracellular ANP were exclusively gamma-ANP, whereas those of BNP were gamma-BNP and its carboxy terminal 45-amino-acid peptide, BNP-45. The ratio of media to cell contents was much higher in BNP than in ANP. Northern blot analysis revealed that both ANP mRNA and BNP mRNA levels were significantly increased by 10(-7) M endothelin (ANP mRNA, +52%; BNP mRNA, +36%; p<0.05 each) and 5 x 10(-5) M 1-oleoyl-2-acetylglycerol (ANP mRNA, +296%; BNP mRNA, +133%; p<0.01 each) but not by 10(-6) M A23187. Thus, the secretion of ANP is stimulated by both the elevation of [Ca2+]i and the activation of protein kinase C, whereas its synthesis is increased mainly by the activation of protein kinase C. The synthesis and secretion of BNP are augmented by the activation of protein kinase C rather than the elevation of [Ca2+]i. Furthermore, the processing and secretion of ANP and BNP may be regulated in different manners.
引用
收藏
页码:1039 / 1048
页数:10
相关论文
共 42 条
[1]   CONCENTRATION AND MOLECULAR-FORMS OF BRAIN NATRIURETIC PEPTIDE IN RAT PLASMA AND SPINAL-CORD [J].
ABURAYA, M ;
SUZUKI, E ;
MINAMINO, N ;
KANGAWA, K ;
TANAKA, K ;
MATSUO, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 177 (01) :40-47
[2]   ISOLATION AND IDENTIFICATION OF RAT-BRAIN NATRIURETIC PEPTIDES IN CARDIAC ATRIUM [J].
ABURAYA, M ;
HINO, J ;
MINAMINO, N ;
KANGAWA, K ;
MATSUO, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 163 (01) :226-232
[3]   DISTRIBUTION AND MOLECULAR-FORMS OF BRAIN NATRIURETIC PEPTIDE IN THE CENTRAL NERVOUS-SYSTEM, HEART AND PERIPHERAL TISSUE OF RAT [J].
ABURAYA, M ;
MINAMINO, N ;
HINO, J ;
KANGAWA, K ;
MATSUO, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 165 (02) :880-887
[4]   BIOSYNTHESIS AND SECRETION OF PROATRIAL NATRIURETIC FACTOR BY CULTURED RAT CARDIOCYTES [J].
BLOCH, KD ;
SCOTT, JA ;
ZISFEIN, JB ;
FALLON, JT ;
MARGOLIES, MN ;
SEIDMAN, CE ;
MATSUEDA, GR ;
HOMCY, CJ ;
GRAHAM, RM ;
SEIDMAN, JG .
SCIENCE, 1985, 230 (4730) :1168-1171
[5]   NEONATAL ATRIA AND VENTRICLES SECRETE ATRIAL-NATRIURETIC-FACTOR VIA TISSUE-SPECIFIC SECRETORY PATHWAYS [J].
BLOCH, KD ;
SEIDMAN, JG ;
NAFTILAN, JD ;
FALLON, JT ;
SEIDMAN, CE .
CELL, 1986, 47 (05) :695-702
[6]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[7]   EFFECT OF MANIPULATIONS OF CA-2+ ENVIRONMENT ON ATRIAL NATRIURETIC FACTOR RELEASE [J].
DEBOLD, ML ;
DEBOLD, AJ .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (06) :H1588-H1594
[8]  
DIETZ JR, 1984, AM J PHYSIOL, V247, P1093
[9]   ENDOTHELIN IS A POTENT SECRETAGOGUE FOR ATRIAL NATRIURETIC PEPTIDE IN CULTURED RAT ATRIAL MYOCYTES [J].
FUKUDA, Y ;
HIRATA, Y ;
YOSHIMI, H ;
KOJIMA, T ;
KOBAYASHI, Y ;
YANAGISAWA, M ;
MASAKI, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 155 (01) :167-172
[10]   ENDOTHELIN STIMULATES ACCUMULATIONS OF CELLULAR ATRIAL NATRIURETIC PEPTIDE AND ITS MESSENGER-RNA IN RAT CARDIOCYTES [J].
FUKUDA, Y ;
HIRATA, Y ;
TAKETANI, S ;
KOJIMA, T ;
OIKAWA, S ;
NAKAZATO, H ;
KOBAYASHI, Y .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 164 (03) :1431-1436