Sabatini S, Kurtzman N A
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock.
Kidney Int. 1988 May;33(5):954-8. doi: 10.1038/ki.1988.93.
The mechanism of action of the thiazide diuretics on calcium transport is not completely understood. The present study was designed to examine the effect of hydrochlorothiazide (HTZ) on Na transport, proton secretion, and Ca45 flux in the turtle bladder, a high resistance membrane. When added to the mucosal solution, 1 mM HTZ had no effect on Na transport or proton secretion, but significantly increased mucosa-to-serosa Ca45 flux at 60 minutes (control 118.9 +/- 39.7 pmol/mg/60 min versus thiazide 286.0 +/- 64.9 pmol/mg/60 min, N = 16, P less than 0.02). In the presence of 5 X 10(-4) M ouabain, a maneuver which inhibits active Na transport, HTZ again significantly enhanced mucosa-to-serosa Ca45 flux. The increment of calcium transport under these conditions was 83.4 +/- 35.2 pmol/mg/60 min (N = 8, P less than 0.05). Mucosal HTZ had no effect on serosa-to-mucosa (that is, bath-to-lumen) Ca45 flux after a 60 minute incubation. Serosal addition of HTZ had no effect on either of the unidirectional Ca45 fluxes or on Na transport. Mucosal tissue Ca45 content was enhanced by HTZ (mucosal) in the presence or absence of ouabain. These results provide support for the view that thiazides have a direct stimulatory effect on calcium absorption at the luminal membrane, perhaps secondary to increased mucosal calcium permeability.
噻嗪类利尿剂对钙转运的作用机制尚未完全明确。本研究旨在考察氢氯噻嗪（HTZ）对龟膀胱（一种高电阻膜）中钠转运、质子分泌及Ca45通量的影响。当将1mM HTZ加入黏膜溶液时，其对钠转运或质子分泌无影响，但在60分钟时显著增加了从黏膜到浆膜的Ca45通量（对照组为118.9±39.7pmol/mg/60分钟，噻嗪组为286.0±64.9pmol/mg/60分钟，N = 16，P＜0.02）。在存在5×10⁻⁴M哇巴因（一种抑制主动钠转运的操作）的情况下，HTZ再次显著增强了从黏膜到浆膜的Ca45通量。在这些条件下钙转运的增加量为83.4±35.2pmol/mg/60分钟（N = 8，P＜0.05）。黏膜HTZ在孵育60分钟后对从浆膜到黏膜（即从浴液到管腔）的Ca45通量无影响。在浆膜侧加入HTZ对单向Ca45通量或钠转运均无影响。无论有无哇巴因，黏膜组织中的Ca45含量均因HTZ（黏膜侧）而增加。这些结果支持了以下观点：噻嗪类药物对腔面膜处的钙吸收有直接刺激作用，这可能继发于黏膜钙通透性的增加。
