Beaumont K, Vaughn D A, Maciejewski A R, Fanestil D D
Department of Medicine, School of Medicine, University of California, San Diego, La Jolla 92093-0623.
Am J Physiol. 1989 Feb;256(2 Pt 2):F329-34. doi: 10.1152/ajprenal.1989.256.2.F329.
Receptors for thiazide diuretic drugs in the rat renal cortex have recently been identified through the binding of [3H]metolazone, a potent diuretic with a thiazide-like mechanism of action. The present studies describe the rapid and reversible alterations that occur in thiazide receptors following acute renal ischemia in the rat. The apparent density of thiazide receptors in kidney membranes as measured by the binding of [3H]metolazone was reduced by 90% following 10 min of renal ischemia produced by clamping the renal pedicle. With release of the clamp and subsequent reperfusion for 10 min, thiazide receptor density returned to within 40% of control levels. Ischemia did not alter apparent affinity of receptors for [3H]-metolazone. Sections prepared from renal cortex and incubated in oxygenated media in vitro displayed similar rapid changes in thiazide receptors. Hypoxia of 10- to 30-min duration produced by incubating sections in vitro in nitrogen-saturated media caused a significant decrease in [3H]metolazone binding that was reversible with return to oxygenated media. Similar decreases were obtained in oxygenated sections that were incubated with mitochondrial inhibitors, dinitrophenol and rotenone, but not in sections incubated with ouabain. These results indicate that renal thiazide receptors undergo a rapid and reversible form of regulation and that controlling mechanisms are dependent on metabolic energy.
最近，通过[3H]美托拉宗（一种作用机制类似噻嗪类的强效利尿剂）的结合，在大鼠肾皮质中鉴定出了噻嗪类利尿药的受体。本研究描述了大鼠急性肾缺血后噻嗪类受体发生的快速且可逆的变化。通过[3H]美托拉宗结合测定的肾膜中噻嗪类受体的表观密度，在夹闭肾蒂导致肾缺血10分钟后降低了90%。松开夹子并随后再灌注10分钟后，噻嗪类受体密度恢复到对照水平的40%以内。缺血并未改变受体对[3H]美托拉宗的表观亲和力。从肾皮质制备并在体外含氧培养基中孵育的切片显示出噻嗪类受体类似的快速变化。通过在氮气饱和培养基中体外孵育切片产生10至30分钟的缺氧，导致[3H]美托拉宗结合显著减少，恢复到含氧培养基后这种减少是可逆的。在用线粒体抑制剂二硝基苯酚和鱼藤酮孵育的含氧切片中也获得了类似的减少，但在用哇巴因孵育的切片中未出现这种情况。这些结果表明，肾噻嗪类受体经历了一种快速且可逆的调节形式，并且控制机制依赖于代谢能量。
