Atrial natriuretic factor binding to its receptor is dependent on chloride concentration: A possible feedback-control mechanism in renal salt regulation.
Atrial natriuretic factor binding to its receptor is dependent on chloride concentration: A possible feedback-control mechanism in renal salt regulation.
复制标题
心房钠尿因子与其受体的结合取决于氯离子浓度：肾盐调节中可能的反馈控制机制。
DOI：
10.1161/01.res.86.11.1135
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发表时间：
2000
影响因子：
20.1
通讯作者：
Misono,KS
中科院分区：
文献类型：
--
作者：
Misono,KS
—尽管大量证据表明心房钠尿因子 (ANF) 在肾盐调节中发挥作用，但其他研究发现在某些生理和病理生理条件下，高血浆 ANF 缺乏钠尿反应。这种对 ANF 明显不敏感的机制尚不清楚。在本研究中，发现 ANF 与其受体的结合需要氯化物的存在，并且以氯化物浓度依赖性方式发生。在 0.1 mol/L NaCl 或其他选定的盐存在下，使用 ANF 受体的纯化重组激素结合结构域测量 ANF 结合。在 NaCl、KCl 或 NH4Cl 存在的情况下检测到高特异性结合。然而，当用 NaHCO3、CH3COONa 或 CH3COONH4 代替盐时，无法检测到结合，这表明结合需要氯化物的存在。牛肾上腺皮质膜制剂中的天然受体也发现了氯依赖性。 ANF 与重组蛋白的结合在 0.05 至 10 mmol/L 范围内依赖于氯化物浓度，并且在约 0.6 mmol/L 当量氯化物浓度时达到半最大结合。在几个固定浓度的 NaCl 下进行的竞争性结合测定表明，降低氯离子浓度会导致最大结合力下降，但不会改变 Kd 值，这表明氯离子的损失会关闭 ANF 结合，而不是降低对 ANF 的亲和力。饱和结合研究表明，过量的 ANF 无法克服低氯引起的结合损失。氯依赖性 ANF 受体结合可能作为反馈控制机制，调节 ANF 受体的作用，从而调节肾钠排泄。
—Although considerable evidence indicates a role for atrial natriuretic factor (ANF) in renal salt regulation, other studies have found a lack of natriuretic response to high-plasma ANF under certain physiological and pathophysiological conditions. The mechanism for this apparent insensitivity to ANF is unknown. In the present study, it was found that ANF binding to its receptor requires the presence of chloride and occurs in a chloride concentration–dependent manner. ANF binding was measured using the purified recombinant hormone-binding domain of the ANF receptor in the presence of 0.1 mol/L NaCl or other selected salt. High specific binding was detected in the presence of NaCl, KCl, or NH4Cl. However, binding was undetectable when the salt was replaced with NaHCO3, CH3COONa, or CH3COONH4, indicating that binding requires the presence of chloride. Chloride dependence was also found with the native receptor in bovine adrenocortical membrane preparations. ANF binding to the recombinant protein was chloride concentration–dependent over a range from 0.05 to 10 mmol/L, and a half-maximum binding was attained at ≈0.6 mmol/L equivalent chloride concentration. Competitive-binding assays at several fixed concentrations of NaCl showed that lowering chloride concentration caused a decrease in maximum binding but did not alterKdvalues, suggesting that a loss of chloride turns off ANF binding rather than reducing affinity for ANF. Saturation-binding studies showed that excess ANF cannot overcome loss of binding caused by low chloride. Chloride-dependent ANF-receptor binding may function as a feedback-control mechanism regulating the ANF-receptor action and, hence, renal sodium excretion.