稳态腹水肿瘤细胞中的氯化钾协同转运。布美他尼是否有抑制作用？

Potassium chloride cotransport in steady-state ascites tumor cells. Does bumetanide inhibit?

作者信息

Aull F

出版信息

Biochim Biophys Acta. 1981 May 6;643(2):339-45. doi: 10.1016/0005-2736(81)90079-1.

Abstract

Bumetanide is a potent diuretic drug which has some structural features in common with furosemide. The steady-state exchange of K+ and Cl- was investigated in Ehrlich ascites tumor cells treated with bumetanide. This agent did not alter the cellular content of K+ or Cl- but the self-exchange of both ions was depressed. K+ self-exchange was inhibited by 55% at bumetanide concentrations as low as 10(-6) M. Cl- self-exchange was less sensitive to this drug but at low concentrations (between 10(-6) and 10(-3) M) bumetanide was a more effective inhibitor of Cl- transfer than furosemide. The steady-state K+ flux of cells equilibrated in NO3- media was compared with the K+ flux in cells treated with 10(-4) or 10(-3) M bumetanide; the Cl(-)-sensitive K+ exchange was equivalent to the bumetanide-sensitive K+ exchange. Since the results suggested that a bumetanide-sensitive (Cl-, K+) cotransport could be operative in steady-state cells, the stoichiometry of the bumetanide-sensitive fluxes was determined by measuring Cl- and K+ fluxes simultaneously in the same cell suspension. At 5 . 10(-4) and 10(-3) M bumetanide concentrations, the ratio of these fluxes was 0.98 +/- 0.07 (S.E.) and 1.04 +/- 0.06, respectively, consistent with the postulated cotransport mechanism. At 10(-4) and 10(-5) M, however, the ratio of the bumetanide-sensitive Cl-/K+ flux was significantly less than 1.0. Since the magnitude of the bumetanide-sensitive K+ flux at 10(-4) M was close to that of the Cl(-)-sensitive flux, a ratio of less than 1.0 at this drug level indicates that Cl-sensitivity and drug sensitivity may not reflect inhibition of the same process under all circumstances.

摘要

布美他尼是一种强效利尿药，它与呋塞米有一些共同的结构特征。在用布美他尼处理的艾氏腹水瘤细胞中研究了钾离子（K⁺）和氯离子（Cl⁻）的稳态交换。该药物并未改变细胞内K⁺或Cl⁻的含量，但两种离子的自身交换均受到抑制。在布美他尼浓度低至10⁻⁶ M时，K⁺自身交换被抑制了55%。Cl⁻自身交换对该药物不太敏感，但在低浓度（10⁻⁶至10⁻³ M之间）时，布美他尼比呋塞米更有效地抑制Cl⁻转运。将在硝酸根（NO₃⁻）培养基中平衡的细胞的稳态K⁺通量与用10⁻⁴或10⁻³ M布美他尼处理的细胞中的K⁺通量进行比较；对Cl⁻敏感的K⁺交换等同于对布美他尼敏感的K⁺交换。由于结果表明布美他尼敏感的（Cl⁻，K⁺）协同转运可能在稳态细胞中起作用，因此通过在同一细胞悬液中同时测量Cl⁻和K⁺通量来确定布美他尼敏感通量的化学计量。在布美他尼浓度为5×10⁻⁴和10⁻³ M时，这些通量的比值分别为0.98±0.07（标准误）和1.04±0.06，这与假定的协同转运机制一致。然而，在10⁻⁴和10⁻⁵ M时，布美他尼敏感的Cl⁻/K⁺通量比值明显小于1.0。由于在10⁻⁴ M时布美他尼敏感的K⁺通量大小接近对Cl⁻敏感的通量大小，在此药物水平下小于1.0的比值表明，在所有情况下，对Cl⁻的敏感性和对药物的敏感性可能并不反映对同一过程的抑制作用。