COMPARISON OF B-1 AND B-2 RECEPTOR ACTIVATION ON INTRACELLULAR CALCIUM, CELL-PROLIFERATION, AND EXTRACELLULAR COLLAGEN SECRETION IN MESANGIAL CELLS FROM NORMAL AND DIABETIC RATS

The mesangial cell is a contractile secreting cell found in a key posi tion in the renal glomerulus. Several kidney and systemic diseases are associated with dysfunctions of the mesangial cells. We compared the effects of bradykinin (BK; B-2 agonist) and des-Arg(9)-bradykinin (DBK ; B-1 agonist) on intracellular calcium mobilization, cell proliferati on, and collagen secretion of mesangial cells from normal and streptoz otocin-induced diabetic rats. Stimulation of mesangial cells with BK a nd DBK caused an increase in intracellular calcium (Ca2+). However, th e patterns of the Ca2+ increases induced by BK and DBK were different, indicating that DBK induced a major Ca2+ influx, whereas BK preferent ially released Ca2+ from intracellular pools. Stimulation with BK and DBK did not show any heterologous desensitization, thus indicating the presence of two distinct binding sites. In normal cells, DBK stimulat ed cell proliferation more than BK, and this action was potentiated by insulin. No effect of BK or DBK was found in cells harvested from dia betic rats. The proliferation effect of BK and DBK was restored by ins ulin. DBK stimulated more collagen synthesis than BK in normal cells. In cells harvested from diabetic rats the collagen secretion was incre ased, but BK and DBK no longer had any effect. Insulin reduced basal c ollagen secretion in normal cells and cells harvested from diabetic ra ts. Insulin also blunted stimulation by BK and DBK in normal cells but did not restore the response to BK and DBK in cells harvested from di abetic rats. Our results show that the sensitivity to DBK and BK decre ases during the course of insulin-dependent diabetes, indicating modul ation by insulin.