Desensitization of inositol phosphate production after agonist stimulation of endothelial cells is not mediated by protein kinase C

To investigate the possible role of protein kinase C activation in the desensitization of inositol phosphate production in endothelial cells we compared desensitization induced by agonists to that induced by the phorbol ester TPA. While histamine or thrombin induced desensitization of inositol phosphate production is homologous TPA induced desensitization is heterologous. The protein kinase C inhibitor H-7 reduced TPA desensitization but had no effect on the agonist induced desensitization. While downregulation of protein kinase C by long term (24 hr) treatment of the cells with TPA reduced the desensitization mediated by short term TPA-treatment it did not affect the agonist induced desensitization. These results suggest that desensitization of inositol phosphate production after agonist stimulation of endothelial cells is not mediated by protein kinase C.