Tyrphostin inhibition of ATP-stimulated DNA synthesis, cell proliferation and fos-protein expression in vascular smooth muscle cells.

摘要: 1. We and others have shown that extracellular ATP (adenosine triphosphate), released from sympathetic nerves platelets, stimulates growth of vascular smooth muscle cells (SMC). To study the importance tyrosine kinases for ATP-mediated proliferation in we used tyrphostins, a recently developed group highly specific inhibitors kinases. 2. induced powerful concentration-dependent increase DNA synthesis measured by [3H]-thymidine incorporation rat aorta SMC (RASMC) an total cell number after 72 h incubation as enzymatic assay. Tyrphostin 25 (10(-5) M) had no effect per se on basal but reduced ATP-stimulated dose-dependent manner. Higher concentrations could not reverse inhibitory tyrphostin 25. The potency several (six) other tyrphostins was also examined found to be slightly greater than with equal efficacy. 3. When RASMC were incubated 10(-5) M 2 h, nearly all (87 +/- 5%) intensely stained antibody Fos protein while controls only 1 2% weakly stained. greatly Fos-protein staining (14 2%). 4. 45Ca(2+)-influx formation inositol phosphates (IPtotal) RASMC. These effects inhibited 5. did alter ATP-induced contraction ring segments aorta. 6. In conclusion, synthesis, expression, 45Ca(2+)-influx, inositolphosphate-production or vasoconstriction. This indicates mitogenic is dependent contrast contractile blood vessels.