OPPOSITE EFFECTS OF CELL-GROWTH FACTORS AND CICLETANINE SULFATE ON THE SODIUM-INDEPENDENT [CL-/HCO3-] EXCHANGE IN CULTURED VASCULAR SMOOTH-MUSCLE

被引：3
作者：
FANOUS, K [1 ]
NAZARET, C [1 ]
SENN, N [1 ]
DECOOPMANMORIN, E [1 ]
ALLARD, M [1 ]
GARAY, RP [1 ]
机构：
[1] FAC MED CRETEIL,CNRS,UA 130251,INSERM,U2,8 RUE GEN SARRAIL,F-94010 CRETEIL,FRANCE
来源：
AMERICAN JOURNAL OF HYPERTENSION | 1993年 / 6卷 / 08期
关键词：
CICLETANINE; CELL GROWTH FACTORS; SULFATES; BICARBONATE; VASCULAR SMOOTH MUSCLE;
D O I：
10.1093/ajh/6.8.674
中图分类号：
R6 [外科学];
学科分类号：
1002 ; 100210 ;
摘要：
Cicletanine sulfate was tested on bicarbonate-dependent pH(i) changes in cultured vascular smooth muscle (A10 line). Cicletanine sulfate exhibited double reactivity with regard to the cell alkalinization induced by bicarbonate uptake. The analysis of 11 concentration-response curves revealed a high reactivity component (IC50 almost-equal-to 3.5 X 10(-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 component (IC50 = 5.9 +/- 2.9 X 10(-7) mol/l; mean +/- SD, n = 7). The high 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 bicarbonate efflux, and the weak-reactivity site corresponds to the inwardly directed sodium-dependent [Cl-/HCO3-] exchanger. Three cell growth factors-epidermal growth factor, arginine-vasopressin, and insulin-were able to stimulate the sodium-independent [Cl-/HCO3-]exchanger in A10 cells. Finally, cicletanine sulfate (30 mumol/L) partially inhibited serum-dependent A10 cell growth. In conclusion, cicletanine sulfate and cell growth factors exert opposite effects (inhibition and stimulation, 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 ability of cicletanine to favorably alter vascular pathology in spontaneously hypertensive rat (SHR) models.
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页码：674 / 679
页数：6
相关论文
共 16 条
[1]  
Auguet M., Guillon J.M., Delaflotte S., Et al., In vivo and in vitro effects of cicletanine in spontaneously hypertensive rats, Drugs under Expl Clin Res, 14, pp. 89-95, (1988)
[2]  
Bouthier J.A., Safar M.E., Deschamps De Paillette E., Tarrade T., Hemodynamic effects of an antihypertensive diuretic substance on the forearm circulation of patients with essential hypertension, Drugs under Expl Clin Res, 14, pp. 221-224, (1988)
[3]  
Chabrier P.E., Guinot P., Tarrade T., Et al., Cicletanine. Car- Diovas Drug Rev, 6, pp. 166-179, (1988)
[4]  
Malherbe E.S., Le Hegarat M., Baranes J., Et al., Comparison of cicletanine with other antihypertensive drugs in SHR- SP models, Drugs under Expl Clin Res, 14, pp. 83-88, (1988)
[5]  
Ruchoux M.M., Droy-Lefaix M.T., Bakri F., Et al., Etudede la protection par le ciclétanine des parois vascularies du rat "Stroke-Prone" spontanément hypertendu, Arch Mal Coeur Et Vaisseaux, 82, pp. 1163-1168, (1989)
[6]  
Tosaki A., Koltai M., Willoughby D.A., Braquet P., Effect of cicletanine on reperfusion-induced arrhythmias and ion shifts in isolated rat hearts, J Cardiovasc Pharmacol, 15, pp. 218-226, (1990)
[7]  
Garay R.P., Rosati C., Nazaret C., Et al., Cicletanine sulfate: Inhibition of anion transport systems and natriuretic activity, Naunyn-Schmiedeberg's Arch Pharmacol, 346, pp. 114-119, (1992)
[8]  
Hadj-Aissa A., Pozet H., Labetin M., Zech P., Site of renal action of cicletanine in man, Diuretics II. Chemistry, Pharmacology and Clinical Applications, pp. 35-37, (1987)
[9]  
Vaughan-Jones R.D., Chloride activity and its control in skeletal and cardiac muscle, Philos Trans R Soc Lond, 299, pp. 537-548, (1982)
[10]  
Gonzalez N.C., Clancy R.L., Catecholamine effect on HC03 /Cl exchange and rabbit myocardial cell pH regulation, Respiration Physiol, 56, pp. 289-299, (1984)
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