Effects of bradykinin on prostaglandin I2 synthesis in human vascular endothelial cells

被引：13

作者：

Yamasaki, S ^{[1
]}

Sawada, S ^{[1
]}

Komatsu, S ^{[1
]}

Kawahara, T ^{[1
]}

Tsuda, Y ^{[1
]}

Sato, T ^{[1
]}

Toratani, A ^{[1
]}

Kono, Y ^{[1
]}

Higaki, T ^{[1
]}

Imamura, H ^{[1
]}

Tada, Y ^{[1
]}

Akamatsu, N ^{[1
]}

Tamagaki, T ^{[1
]}

Tsuji, H ^{[1
]}

Nakagawa, M ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Med 2, Kamigyo Ku, Kyoto 6028566, Japan

来源：

HYPERTENSION | 2000年 / 36卷 / 02期

关键词：

bradykinin; prostacyclin; kinetics; calcium; phospholipases A; prostaglandin H synthase; polymerase chain reaction;

D O I：

10.1161/01.HYP.36.2.201

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

The effects of bradykinin on the regulatory mechanisms of prostacyclin synthesis in endothelial cells were investigated in association with intracellular Ca2+ kinetics, cytosolic phospholipase A(2) (cPLA(2)) activity, and mRNA expression of cPLA(2) and prostaglandin H synthase (PGHS) isoforms. Bradykinin enhanced prostacyclin release from endothelial cells time-dependently, but pretreatment with EGTA H-7 or HOE 140 inhibited bradykinin-induced prostacyclin release, Bradykinin increased both the influx of extracellular Ca2+ and Ca2+ release from the intracellular Ca2+ storage sites. These reactions occurred within 5 minutes after bradykinin stimulation. Within 15 minutes, bradykinin activated cPLA(2) to 1.3-fold the control level. The constitutive expressions of mRNA of cPLA(2), PGHS-1. and PGHS-2 was 87, 562, and 47 amol/mu g RNA, respectively. With the stimulation of bradykinin, cPLA(2) mRNA increased to 746 amol/mu g RNA in 15 minutes, PGHS-1 mRNA increased to 10 608 amol/mu g RNA, and PGHS-2 mRNA increased to 22 400 amol/mu g RNA in 180 minutes. Pretreatment with cycloheximide superinduced cPLA(2) and PGHS-2 mRNA expression but almost completely inhibited PGHS-1. Pretreatment with EGTA had effects similar to pretreatment with cycloheximide in the case of cPLA(2) and PGHS-1 but did not affect PGHS-2. These findings suggest that the elevation of cPLA(2) activity caused by the increase of intracellular Ca2+ concentration is important in the early phase of bradykinin-induced prostacyclin synthesis and that the mechanisms regulating cPLA(2) are different from those regulating PGHS isoforms in endothelial cells.

引用

页码：201 / 207

页数：7

共 20 条

[1]

Brown NJ, 1996, J PHARMACOL EXP THER, V279, P703

[2] ORAL ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR IN LONG-TERM TREATMENT OF HYPERTENSIVE PATIENTS [J].

BRUNNER, HR ;

GAVRAS, H ;

WAEBER, B ;

KERSHAW, GR ;

TURINI, GA ;

VUKOVICH, RA ;

MCKINSTRY, DN ;

GAVRAS, I .

ANNALS OF INTERNAL MEDICINE, 1979, 90 (01) :19-23

[3]

CHANNON JY, 1990, J BIOL CHEM, V265, P5409

[4] A NOVEL ARACHIDONIC ACID-SELECTIVE CYTOSOLIC PLA2 CONTAINS A CA2+-DEPENDENT TRANSLOCATION DOMAIN WITH HOMOLOGY TO PKC AND GAP [J].

CLARK, JD ;

LIN, LL ;

KRIZ, RW ;

RAMESHA, CS ;

SULTZMAN, LA ;

LIN, AY ;

MILONA, N ;

KNOPF, JL .

CELL, 1991, 65 (06) :1043-1051

[5]

GENG Y, 1995, J IMMUNOL, V155, P796

[6]

GRYNKIEWICZ G, 1985, J BIOL CHEM, V260, P3440

[7] A GENERAL-METHOD OF INVITRO PREPARATION AND SPECIFIC MUTAGENESIS OF DNA FRAGMENTS - STUDY OF PROTEIN AND DNA INTERACTIONS [J].

HIGUCHI, R ;

KRUMMEL, B ;

SAIKI, RK .

NUCLEIC ACIDS RESEARCH, 1988, 16 (15) :7351-7367

[8] Protein-tyrosine-kinase-dependent expression of cyclo-oxygenase-1 and -2 mRNAs in human endothelial cells [J].

Hirai, K ;

Takayama, H ;

Tomo, K ;

Okuma, M .

BIOCHEMICAL JOURNAL, 1997, 322 :373-377

[9] HUMAN CYCLOOXYGENASE-2 CDNA [J].

HLA, T ;

NEILSON, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (16) :7384-7388

[10] MEASUREMENT OF INTERLEUKIN-1 STIMULATED CONSTITUTIVE PROSTAGLANDIN G/H SYNTHASE (CYCLOOXYGENASE) MESSENGER-RNA LEVELS IN OSTEOBLASTIC MC3T3-E1 CELLS USING COMPETITIVE REVERSE-TRANSCRIPTASE POLYMERASE CHAIN-REACTION [J].

KAWAGUCHI, H ;

YAVARI, R ;

STOVER, ML ;

ROWE, DW ;

RAISZ, LG ;

PILBEAM, CC .

ENDOCRINE RESEARCH, 1994, 20 (03) :219-233

← 1 2 →