EFFECTS OF THE SELECTIVE PROTEIN-KINASE-C INHIBITOR RO-31-7549 ON HUMAN ANGIOTENSIN-II RECEPTOR DESENSITIZATION AND INTRACELLULAR CALCIUM-RELEASE

The mechanism underlying type I angiotensin II (Ang II) receptor (AT1 receptor) desensitisation is unknown. Structural features suggest it m ay be a substrate for protein kinase C (PKC). The effects of a selecti ve PKC inhibitor, Ro 31-7539, on receptor desensitisation were investi gated in CHO cells expressing the human AT1 receptor. Desensitisation was demonstrated with respect to the calcium response to Ang II in Fur a-2-loaded cells. Ro 31-7549 had no effect on desensitisation. However , pretreatment with Ro 31-7519 caused a dose-dependent reduction in ca lcium release from intracellular stores. PKC may therefore act at a lo cus distal from the receptor itself.