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
Jp. Girolami et al., 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, Canadian journal of physiology and pharmacology, 73(7), 1995, pp. 848-853
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.