Abstract
The objective of this study was to determine whether the G-protein-linked angiotensin II receptor mediated inositol phosphate production involves a tyrosine phosphorylation (tyr phos) dependent pathway in the heart. Cardiomyocytes, in culture, from 7-day-old chick embryonic hearts were incubated with myo [3H] inositol for 18-24 h. Cells were incubated with LiCl to inhibit inositol 1-phosphate phosphatase and allow accumulation of inositol phosphates with angiotensin II (ang II) treatment. Inositol fractions were separated on column chromatography. Ang II produced significant (p < 0.01) increases of InsP1, InsP2, and InsP3, within 1 min of treatment of cardiomyocytes. Tyrosine kinase inhibition with genistein significantly (p < 0.05) reduced ang II induced inositol phosphate production. This did not occur with the analogue diazdien that is a very weak inhibitor of tyrosine kinase. The ability of ang II to induce tyr phos was demonstrated in whole cell lysates of cardiomyocytes immunoprecipitation with anti-P-Tyr antibodies. Genistein blunted this action of ang II. The rapid activation of a tyr phos dependent pathway by ang II was demonstrated by the similar time course of tyr phos of two different cardiac proteins, 70 and 195 kD...Continue Reading
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