Desensitization of angiotensin-stimulated inositol phosphate accumulation in human vascular smooth muscle cells.

The effect of angiotensin II treatment on desensitization of phospholipase C (PLC)-mediated inositol phosphate accumulation has not been quantitated in human aortic vascular smooth muscle (HVSM) cells. We determined the angiotensin II pretreatment dose dependency and time course for desensitization of PLC activation in HVSM cells and the effect of protein kinase C (PKC) activators on angiotensin II-mediated inositol phosphate accumulation. Our results with PKC activators and direct G protein stimulators suggest that PKC activation may play a negative feedback role in desensitization of angiotensin II-activated signaling in HVSM cells by modifying the Gq transducer, PLC-beta effector, or related proteins in the signaling pathway. However, neither angiotensin II nor PKC activator affected basal phosphorylation levels of PLC-beta1 or PLC-beta3 in HVSM cells; PLC-beta isoenzymes were shown to be phosphorylated in unstimulated cells independent of PKC inhibition. We suggest that desensitization of G protein-stimulated inositol phosphate accumulation in HVSM differs from other cell types in which phosphorylation of PLC-beta isoenzymes accompanies desensitization.