Regulation of transepithelial transport in the distal nephrons through interacting hormonal actions from the luminal and basolateral side.

多巴胺（DA）引起尿钠。皮质收集管（COD）被认为是负责这一作用的一个部位。以往的研究报道CCD中存在Di-like或D2-like受体，但关于受体亚型在集管中介导多巴胺作用存在争议。为了解决这个问题，采用体外微灌注技术，测量经上皮电压（Vt, mV）来表征多巴胺受体的亚型。在家兔中，1 nM至10 muM基底侧DA诱导了剂量依赖性的vt去极化。用选择性d2样受体拮抗剂多潘立酮预处理可消除DA去极化。相比之下，选择性di样受体拮抗剂SCH23390未能阻断da诱导的Vt改变。此外，选择性d2样受体激动剂SKF81297对Vt无明显去极化作用，而选择性d2样受体激动剂溴隐亭可引起显著的Vt变化，且呈剂量依赖性。10 ~ 100 ma的腔内DA也能显著去极化Vt。前处理的腔内SCH23390完全阻断了腔内DA诱导的去极化。相比之下，多潘立酮未能抑制腔内DA诱导的去极化。此外，SKF81297的作用类似于DA的作用，而溴隐亭的作用则不显著。因此，DA受体存在于CCD上皮的两侧，但受体亚型不同：基底侧DA-2样受体和基底侧DA-1样受体。就DA的利钠作用而言，基底外侧DA被认为发挥了主要作用，因为基底外侧DA诱导的去极化被基底外侧乌巴因或管腔阿米洛胺阻断，并且管腔到浴液的22Na通量确实被基底外侧DA抑制。另一方面，管腔DA受体的参与是值得怀疑的，因为它对DA的敏感性较低（需要10muM DA才能显着去极化），而且去极化本身也比基底侧DA诱导的去极化小。少

Dopamine (DA) causes natriuresis. Cortical collecting duct (COD) has been suggested to be a site responsible for this action. Previous studies reported the existence of either Di-like or D2-like receptor in the CCD and there is a controversy regarding the receptor subtype mediating in the dopanilne action in the collecting duct.To approach this ciuestion, the subtype of dopamine receptors was characterized by using in vitro microperfusion technique, measuring transepithelial voltage (Vt, mV). In the rabbit, 1 nM to 10 muM basolateral DA induced a dose dependent depolarization of Vt.Pretreatment with domperidone, a selective D2-like receptor antagonist, abolished DA depolarization. In contrast, SCH23390, a selective Di-like receptor antagonist, failed to block the DA-induced Vt change. Furthermore, while SKF81297, a selective D1-hke receptor agonist, did not significantly depolarized Vt, bromocriptine, a selective D2-like receptor agonist, caused significant Vt change in a dose dependen … More t manner. 10 to 100 muM luminal DA also depolarized Vt significantly. Pre-treatment of luminal SCH23390 completely blocked the luminal DA induced depolarization. In contrast1 luminal domperidone failed to suppress the luminal DA induced depolarization. Further luminal SKF81297 mimicked the effect of luminal DA, while luminal bromocriptine had no significant effect. Thus, DA receptors reside on both sides of the CCD epithelium but the receptor subtypes are distinct : basolaterally DA-2 like receptors and lurninally DA-1 like receptors. In terms of the natriuretic action of DA, basolateral DA was thought to play a major role, since basolateral DA-induced depolarization was blocked by basolateral ouabain or luminal amiloride, and lumen-to-bath 22Na flux was indeed suppressed by basolateral DA.On the other hand, the participation of luminal DA receptor was questionable since it was less sensitive to DA (require 10muM DA for significant depolarization) and the depolarization itself was also smaller than that induced by basolateral DA. Less