Bradykinin-induced inhibition of cell proliferation and tyrosine kinase activity in rat mesangial cells

The relationship between cell proliferation, protein tyrosine phosphorylati on, phosphotyrosine kinase activity and bradykinin receptor activation in r at mesangial cells was investigated. We demonstrated that bradykinin (BK), through the B2 receptor, induced a dose-dependent inhibition of mesangial c ell proliferation stimulated by fetal calf serum. We next found that BK ind uced a dose-dependent inhibition of phospho-tyrosine kinase activity. Treat ments with pertussistoxin, inhibition of phospholipase C and protein kinase C inhibitors and chelation of free cytosolic calcium did not change the br adykinin-induced inhibition of phosphotyrosine kinase. Western blot analysi s of phosphotyrosinated proteins demonstrated that BK reduced tyrosine phos phorylation of several proteins among which we identified the 125-focal adh esion kinase. Taken together, these data suggest for the first time that, i n proliferating rat mesangial cells, B2 receptor stimulation is able to ind uce, via a pertussis insensitive pathway, the inhibition of tyrosine kinase activity and mesangial cell proliferation.