Okadaic acid inhibits angiotensin II stimulation of Ins(1,4,5)P3 and calcium signalling in rat hepatocytes

FEBS Letters

Mattingly, Raymond R.¹  Garrison, James C.¹ 

[1] Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA

关键词: Okadaic acid;    Angiotensin II;    Calcium ion concentration;    Intracellular;    Inositol phosphate;    Inositol 1;    4.5-trisphosphate 3-kinase;    Rat hepatocyle;    OKA;    okadaic acid;    CL-A;    calyculin A;    [Ca2+]i;    intracellular calcium concentration;    Ins(1;    4;    5)P3;    inositol 1;    4;    5-trisphosphate;    Ins(1;    3;    4)P3;    inositol 1;    3;    4-trisphosphate;    Ins(I.3;    4;    5)P4;    inositol 1;    3.4;    5-tetrakisphosphate;    cBSA;    crystalline bovine serum albumin;    KRB;    Krebs-Ringer bicarbonate;    pH 7.4;    DMSO;    dimethylsulphoxide;    HPLC;    high-pressure liquid chromatography;   

DOI  :  10.1016/0014-5793(92)80385-T

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

OKA² and CL-A significantly inhibit the ability of angiotensin II, ATP and vasopressin to raise [Ca²⁺]_i in rat hepatocytes, with a partial inhibition of the initial spike, and a complete inhibition of the following plateau. In contrast, the [Ca²⁺]_i response to thapsigargin, which releases intracellular calcium stores through a mechanism independent of inositol phosphates, is much less affected. The ability of angiotensin II to stimulate Ins(1.4.5)P₃ production is also reduced by OKA, with kinetics consistent with the inhibited [Ca²⁺], response. Since OKA and CL-A are potent and selective inhibitors or phosphoprotein phosphatases. these results provide further evidence that agonist-stimulated Ins(1,4,5)P₃ signalling can be inhibited by protein phosphorylation.

【 授权许可】

Unknown