Ziyadeh F N, Kelepouris E, Agus Z S
Biochim Biophys Acta. 1987 Feb 12;897(1):52-6. doi: 10.1016/0005-2736(87)90314-2.
Thiazides inhibit voltage-independent NaCl absorption in the urinary bladder of the winter flounder presumably by blocking an electroneutral mucosal Na/Cl co-transporter. As thiazides stimulate calcium absorption in mammalian distal convoluted tubule while inhibiting NaCl absorption, we studied the effects of hydrochlorothiazide (HCTZ) on unidirectional 45Ca fluxes and intracellular electrical potential in short-circuited bladders to examine possible mechanisms of HCTZ effects on calcium transport. Basal secretory calcium flux was, on average, slightly larger than absorptive flux, reflecting small net calcium secretion. Mucosal addition of HCTZ (10(-4) M) stimulated absorptive calcium flux by 46% while the secretory flux was unaltered. Thus, HCTZ tended to induce net calcium absorption. Pre-treatment with serosal ouabain (10(-4) M) attenuated the HCTZ-induced increase in absorptive calcium flux. Moreover, HCTZ hyperpolarized the mucosal membrane potential by 18% as measured by conventional open-tip microelectrodes. These effects of HCTZ are consistent with the hypothesis that HCTZ indirectly stimulates Na/Ca exchange located at the serosal membrane. In conclusion, HCTZ in flounder urinary bladder, as in mammalian distal convoluted tubule, simultaneously inhibits NaCl absorption and stimulates calcium absorption. This study expands on the functional similarities between the flounder urinary bladder and the mammalian distal convoluted tubule.
噻嗪类药物可能通过阻断电中性的黏膜钠/氯共转运体，抑制了冬比目鱼膀胱中不依赖电压的氯化钠吸收。由于噻嗪类药物在抑制哺乳动物远曲小管氯化钠吸收的同时会刺激钙吸收，我们研究了氢氯噻嗪（HCTZ）对短路膀胱中单向45Ca通量和细胞内电位的影响，以探讨HCTZ影响钙转运的可能机制。基础分泌性钙通量平均略大于吸收性通量，反映出少量的净钙分泌。黏膜添加HCTZ（10^(-4) M）可使吸收性钙通量增加46%，而分泌性通量未改变。因此，HCTZ倾向于诱导净钙吸收。用浆膜哇巴因（10^(-4) M）预处理可减弱HCTZ诱导的吸收性钙通量增加。此外，用传统的开口尖端微电极测量，HCTZ使黏膜膜电位超极化18%。HCTZ的这些作用与HCTZ间接刺激位于浆膜的钠/钙交换这一假设一致。总之，比目鱼膀胱中的HCTZ与哺乳动物远曲小管中的情况一样，同时抑制氯化钠吸收并刺激钙吸收。本研究扩展了比目鱼膀胱与哺乳动物远曲小管之间的功能相似性。
