Amiloride-sensitive regulation of intracellular pH in B-cells: activation by glucose.

Amiloride-sensitive regulation of intracellular pH in B-cells: activation by glucose.
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B 细胞内 pH 值的阿米洛利敏感调节:葡萄糖激活。

DOI:
10.1016/0026-0495(86)90120-4
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发表时间:
1986
期刊:
Metabolism: clinical and experimental
影响因子:
--
通讯作者:
Tarvin,JT
Tarvin,JT
中科院分区:
--
文献类型:
--
作者:
Pace,CS;Tarvin,JT

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葡萄糖代谢产生的细胞内pH(pHi)的改变被认为是一种转导装置,用于控制B细胞质膜中K+电导的变化,导致与尖峰活动相关的膜电位的去极化和周期性变化。渗透性弱酸或弱碱和阿米洛利抑制H+挤出的Na:H交换对葡萄糖诱导的电活动的影响表明,电事件是pH敏感的。为了证明这些条件改变pHi,我们使用[14 C] DMO测定了葡萄糖、丙酸和NH 4Cl在存在或不存在阿米洛利的情况下对大鼠胰岛pHi的影响。葡萄糖浓度为2.8 mmol/L时,pHi降低0.09单位(pHi= 7.08 ± 0.01,M ± SEM),葡萄糖浓度为16.7 mmol/L时pHi降低0.19单位。葡萄糖剂量相关的pH降低在4 mmol/L时产生半最大反应。加入0.1mmol/L阿米洛利对无葡萄糖时的pH值无影响,而在2.8mmol/L葡萄糖存在时,使pH值降低0.14单位。在2.8 mmol/L葡萄糖中加入20 mmol/L丙酸可使pH降至6.85 ± .05,而20 mmol/L NH 4Cl可使pH升至7.27 ± .07。阿米洛利的加入不能进一步降低由20 mmol/L丙酸或16.7 mmol/L葡萄糖引起的pH降低。这些结果表明,阿米洛利敏感的Na:H交换在调节pH值中起着重要作用,但存在另一种pH调节方式来补偿酸负荷条件下Na:H交换的抑制。
Alterations in intracellular pH (pHi) generated by metabolism of glucose has been proposed to be a transduction device for controlling changes in K+conductance in the plasma membrane of the B-cell leading to depolarization and cyclic variations in the membrane potential associated with spike activity. The influence of permeable weak acids or bases and amiloride inhibition of H+extrusion by a Na:H exchanger on glucose-induced electrical activity has suggested that the electrical events are pH-sensitive. In order to document that these conditions alter pHi, we determined the influence of glucose, propionic acid, and NH4Cl, in the presence or absence of amiloride on pHiof rat islets using [14C] DMO. Glucose, 2.8 mmol/L decreased pHiby .09 unit compared to the absence of glucose (pHi= 7.08 ± .01, M ± SEM) and 16.7 mmol/L glucose reduced pHiby .19 unit. The glucose dose-related decrease in pHiyielded a half-maximal response at 4 mmol/L. The addition of 0.1 mmol/L amiloride had no influence on pHiwithout glucose and decreased pHiin the presence of 2.8 mmol/L glucose by .14 unit. The addition of 20 mmol/L propionic acid to 2.8 mmol/L glucose reduced pHito 6.85 ± .05, whereas 20 mmol/L NH4Cl increased pHito 7.27 ± .07. The addition of amiloride did not further lower the reduction in pHielicited by 20 mmol/L propionic acid or 16.7 mmol/L glucose. These results suggest that the amiloride-sensitive Na:H exchanger plays a major role in regulation of pHi, but another modality for pHiregulation exists to compensate for inhibition of Na:H exchange under conditions of an acid load.