CGMP ANTAGONIZES ANGIOTENSIN-MEDIATED PHOSPHATIDYLCHOLINE HYDROLYSIS AND C-KINASE ACTIVATION IN MESANGIAL CELLS

被引:16
作者
BARNETT, RL [1 ]
RUFFINI, L [1 ]
RAMSAMMY, L [1 ]
PASMANTIER, R [1 ]
FRIEDLAENDER, MM [1 ]
NORD, EP [1 ]
机构
[1] SUNY STONY BROOK, NORTHPORT VET AFFAIRS MED CTR, STONY BROOK, NY 11794 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 1995年 / 268卷 / 02期
关键词
PROTEIN KINASE C; PHOSPHOLIPASE C; PHOSPHOLIPASE D; GUANOSINE3'; 5'-CYCLIC MONOPHOSPHATE; ATRIAL NATRIURETIC FACTOR;
D O I
10.1152/ajpcell.1995.268.2.C376
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Previous studies from this laboratory have shown that in cultured rat mesangial cells (MC), angiotensin II (ANG II) mediates its effects via activation of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D (PC-PLD). In addition, guanosine 3',5'-cyclic monophosphate (cGMP)-elevating maneuvers that stimulate particulate and soluble guanylate cyclase [atrial natriuretic factor (ANF) and sodium nitroprusside (SNP), respectively] antagonize ANG II-mediated PI-PLC activation. The current study explored whether cGMP impairs ANG II-mediated PC-PLC and PLD activity. The ANG II-stimulated release of the water-soluble metabolites of PC breakdown (phosphorylcholine and choline) was blocked by ANF and SNP. ANG II-stimulated phosphatidic acid and phosphatidylethanol formation were significantly reduced by ANF and SNP, confirming that cGMP blunted PLD activity. The inhibitory effect of cGMP on PLD could be reversed by N-(2-[methylamino]ethyl)5-isoquinolinesulfonamide, a blocker of cGMP-dependent protein kinase. In parallel experiments, ANF and SNP abrogated sustained diacylglycerol (DAG) accumulation derived from ANG II stimulation of PC hydrolysis, confirming that cGMP diminished PC-PLC activity. Inhibition of PC-derived DAG accumulation by cGMP was associated with a concomitant decrement in ANG II-mediated translocation of protein kinase C (PKC) activity from the cytosol to the membrane. In summary, in MC, cGMP antagonizes ANG II-mediated PC hydrolysis, DAG formation, and PKC activation. We propose that cGMP-mediated inhibition of phospholipid metabolism and PKC translocation plays an important role in MC vasorelaxation.
引用
收藏
页码:C376 / C381
页数:6
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