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SYMPOSIUM: Experimental Biology 1995 Role of Mesangial Cell Ion Transport in Glomerular Physiology and Disease: ANGIOTENSIN II‐INDUCED TYROSINE PHOSPHORYLATION IN MESANGIAL AND VASCULAR SMOOTH MUSCLE CELLS
Author(s) -
Marrero Mario B,
Schieffer Bernhard,
Bernstein Kenneth E,
Ling Brian N
Publication year - 1996
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1996.tb03067.x
Subject(s) - tyrosine phosphorylation , protein tyrosine phosphatase , vascular smooth muscle , phosphorylation , angiotensin ii , endocrinology , mesangial cell , medicine , tyrosine , sodium orthovanadate , biology , genistein , phospholipase c , tyrosine kinase , intracellular , signal transduction , microbiology and biotechnology , biochemistry , kidney , smooth muscle , blood pressure
SUMMARY1 Angiotensin II (AngII)‐induced, activation of phospholipase C (PLC) and Ca 2+ ‐dependent Cl − channels is an important signal transduction pathway for the regulation of vascular smooth muscle cell (VSMC) and glomerular mesangial cell contraction and growth. While AT receptors are traditionally thought to be G‐protein coupled to the β isoform of PLC, recent evidence suggests that in some tissues AT receptors may also activate the PLC‐γ isoform via tyrosine phosphorylation. 2 By western analysis, we identified PLC‐γ1 in the above cell types. We found that within 3 min of exposure to 10 −7 mol/L AngII, tyrosine phosphorylation of PLC‐γ1 was observed; however, peak response (> 3‐fold increase) occurred within 0.5 min. In addition, pre‐incubation of these cells with the tyrosine kinase inhibitor genistein blocked the tyrosine phosphorylation of PLC‐γ1 by AngII. In contrast, preincubation with the tyrosine phosphatase inhibitor sodium vanadate increased the levels of tyrosine phosphorylation of PLC‐γ1. Similar results were found when intracellular levels of 1,4,5‐IP 3 were measured after AngII exposure. 3 By using patch clamp techniques on cultured rat mesangial cells exposed to AngII, we found that the release of 1,4,5‐IP 3 ‐sensitive intracellular Ca 2+ stores stimulated low conductance Cl − channels. Preincubation with genistein, abolished the usual 10‐fold increase in Cl − channel activity observed with AngII. 4 Therefore, we conclude that in VSMC and glomerular mesangial cells (i) AngII transiently stimulates PLC activity via tyrosine phosphorylation of the γ1 isoenzyme, (ii) tyrosine phosphorylation of PLC‐γ1 and production of 1,4,5‐IP 3 in response to AngII is dramatically inhibited by tyrosine kinase inhibition and stimulated by tyrosine phosphatase inhibition, (iii) activation of Ca 2+ ‐dependent Cl − channels by AngII‐induced release of 1,4,5‐IP 3 ‐dependent intracellular Ca 2+ stores is also abolished by tyrosine kinase inhibition. In summary, this AngII‐induced signal transduction cascade provides a possible mechanism for both the contractile and growth‐stimulating effects of AngII on VSMC and glomerular mesangial cells.