K. Fanous et al., OPPOSITE EFFECTS OF CELL-GROWTH FACTORS AND CICLETANINE SULFATE ON THE SODIUM-INDEPENDENT [CL- HCO3-] EXCHANGE IN CULTURED VASCULAR SMOOTH-MUSCLE/, American journal of hypertension, 6(8), 1993, pp. 674-679
Cicletanine sulfate was tested on bicarbonate-dependent pH(i) changes
in cultured vascular smooth muscle (A10 line). Cicletanine sulfate exh
ibited double reactivity with regard to the cell alkalinization induce
d by bicarbonate uptake. The analysis of 11 concentration-response cur
ves revealed a high reactivity component (IC50 almost-equal-to 3.5 X 1
0(-8) mol/L) and a weak reactivity component (IC50 almost-equal-to 4 X
10(-4) ml/L). Regarding the cell acidification induced by bicarbonate
extrusion, cicletanine sulfate exhibited a single high reactivity com
ponent (IC50 = 5.9 +/- 2.9 X 10(-7) mol/l; mean +/- SD, n = 7). The hi
gh and weak reactivity sites were both sensitive to DIDS. Analysis of
the data strongly suggested that the highly reactive site corresponds
to a sodium-independent (Cl-/HCO3-] exchanger, which catalyzes net bic
arbonate efflux, and the weak-reactivity site corresponds to the inwar
dly directed sodium-dependent [Cl-/HCO3-] exchanger. Three cell growth
factors-epidermal growth factor, arginine-vasopressin, and insulin-we
re able to stimulate the sodium-independent [Cl-/HCO3-]exchanger in A1
0 cells. Finally, cicletanine sulfate (30 mumol/L) partially inhibited
serum-dependent A10 cell growth. In conclusion, cicletanine sulfate a
nd cell growth factors exert opposite effects (inhibition and stimulat
ion, respectively) on the sodium-independent [Cl-/HCO3-] exchanger in
cultured vascular smooth muscle. The effect of cicletanine sulfate on
the sodium-independent [Cl-/HCO3-] exchanger may account for the abili
ty of cicletanine to favorably alter vascular pathology in spontaneous
ly hypertensive rat (SHR) models.