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

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+]i response. Since OKA and CL-A are potent and selective inhibitors of phosphoprotein phosphatases, these results provide further evidence that agonist-stimulated Ins(1,4,5)P3 signalling can be inhibited by protein phosphorylation.