Abstract
Protein kinase C activity towards exogeneous histone was found in a cytosolic fraction of rat renal mesangial cells. The analysis of the 100 000 × g supernatant fraction with DEAE-cellulose ion-exchange chromatography gave a protein kinase C preparation that was dependent on Ca 2+ and phosphatidylserine for its activity. The addition of diolein decreased the Ca 2+ requirement of the enzyme. 1-(5-Isoquinoline-sulfonyl)-2-methylpiperazine (H-7), sphingosine and cytotoxin I potently inhibited the protein kinase C activity prepared from mesangial cells as well as the 12- O-tetradecanoylphorbol 13-acetate (TPA)-induced prostaglandin synthesis in intact mesangial cells. In the second part of the study, the desensitization of angiotensin II-stimulated phospholipase C activity was investigated. Angiotensin II induced a rapid increase in inositol trisphosphate (IP 3) formation. Pretreatment of cells with angiotensin II, followed by removal of the hormone, resulted in a decreased response to a second application of angiotensin II. A similar protocol involving pretreatment with angiotensin II had no effect on subsequent responsiveness to [Arg 8]vasopressin. The specific antagonist [Sar 1, Ala 8]angiotensin II did not stimulate IP 3 formation neither did it inhibit the response to a subsequent stimulation with angiotensin II. After angiotensin II pretreatment, a prolonged incubation (120 min) restored responsiveness of the cells to angiotensin II. Pretreatment of mesangial cells with H-7, sphingosine or cytotoxin I almost completely diminished the desensitization of angiotensin II-stimulated IP 3 generation. These results indicate that, in rat mesangial cells, angiotensin II induces a homologous desensitization of phospholipase C stimulation. It is proposed that protein kinase C activation plays an important role in the molecular mechanism of desensitization of angiotensin II-stimulated polyphosphoinositide metabolism.
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Schedule a callMore From: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
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