Anti-mitogenic effects of sarpogrelate in cultured rat mesangial cells

被引:8
作者
Eto, Y [1 ]
Nitta, K [1 ]
Uchida, K [1 ]
Tsutsui, T [1 ]
Natori, K [1 ]
Kawashima, A [1 ]
Yumura, W [1 ]
Nihei, H [1 ]
机构
[1] TOKYO WOMENS MED COLL, KIDNEY CTR, DEPT MED, SHINJUKU KU, TOKYO 162, JAPAN
关键词
sarpogrelate; serotonin; DNA synthesis; mesangial cells; cell cycle;
D O I
10.1016/S0024-3205(97)00018-0
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
We investigated the effects of the new 5-HT2A receptor antagonist, sarpogrelate, on DNA synthesis in renal mesangial cells stimulated with 5-HT in the presence and absence of platelet-derived growth factor (PDGF)-BB. Both 5-HT and PDGF-BB demonstrated a mitogenic effect on these cells. When mesangial cells were incubated in the absence of PDGF-BB, sarpogrelate inhibited DNA synthesis in these cells in a dose-dependent manner. In the presence of PDGF-BB, sarpogrelate had a weaker anti-mitogenic effect in mesangial cells stimulated with 5-HT. Sarpogrelate was cytotoxic at concentrations over 10(-5) M according to the results of LDH release assays, and it reduced the S1 phase in mesangial cells stimulated with 5-HT by a flow cytometry. These findings suggest that sarpogrelate may be effective in the treatment of some glomerulonephritis associated with mesangial cell proliferation.
引用
收藏
页码:PL193 / PL199
页数:7
相关论文
共 16 条
[1]  
CAMERON JS, 1984, ANNU REV MED, V35, P175, DOI 10.1146/annurev.med.35.1.175
[2]   RAPID, ONE-STEP STAINING PROCEDURES FOR ANALYSIS OF CELLULAR DNA AND PROTEIN BY SINGLE AND DUAL LASER FLOW-CYTOMETRY [J].
CRISSMAN, HA ;
STEINKAMP, JA .
CYTOMETRY, 1982, 3 (02) :84-90
[3]  
KASHGARIAN M, 1985, LAB INVEST, V52, P569
[4]   SYNTHESES AND PLATELET-AGGREGATION INHIBITORY AND ANTITHROMBOTIC PROPERTIES OF [2-[(OMEGA-AMINOALKOXY)PHENYL]ETHYL]BENZENES [J].
KIKUMOTO, R ;
HARA, H ;
NINOMIYA, K ;
OSAKABE, M ;
SUGANO, M ;
FUKAMI, H ;
TAMAO, Y .
JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (06) :1818-1823
[5]   GLOMERULAR CELLS IN CULTURE [J].
KREISBERG, JI ;
KARNOVSKY, MJ .
KIDNEY INTERNATIONAL, 1983, 23 (03) :439-447
[6]   PHYSIOLOGY OF THE MESANGIAL CELL [J].
MENE, P ;
SIMONSON, MS ;
DUNN, MJ .
PHYSIOLOGICAL REVIEWS, 1989, 69 (04) :1347-1424
[7]   SEROTONIN AND THE GLOMERULAR MESANGIUM - MECHANISMS OF INTRACELLULAR SIGNALING [J].
MENE, P ;
PUGLIESE, F ;
CINOTTI, GA .
HYPERTENSION, 1991, 17 (02) :151-160
[8]   STIMULATION OF AORTIC SMOOTH-MUSCLE CELL MITOGENESIS BY SEROTONIN [J].
NEMECEK, GM ;
COUGHLIN, SR ;
HANDLEY, DA ;
MOSKOWITZ, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (03) :674-678
[9]   GLOMERULAR ENDOTHELIAL-CELLS PROMOTE MESANGIAL CELL-GROWTH VIA A PDGF-LIKE SUBSTANCE [J].
NITTA, K ;
UCHIDA, K ;
TSUTSUI, T ;
KAWASHIMA, A ;
YUMURA, W ;
NIHEI, H .
LIFE SCIENCES, 1994, 56 (03) :143-150
[10]   INTERLEUKIN-6 IS AN AUTOCRINE GROWTH-FACTOR FOR MESANGIAL CELLS [J].
RUEF, C ;
BUDDE, K ;
LACY, J ;
NORTHEMANN, W ;
BAUMANN, M ;
STERZEL, RB ;
COLEMAN, DL .
KIDNEY INTERNATIONAL, 1990, 38 (02) :249-257