Ruggles B T, Murayama N, Werness J L, Gapstur S M, Bentley M D, Dousa T P
J Clin Endocrinol Metab. 1985 May;60(5):914-21. doi: 10.1210/jcem-60-5-914.
The major tubular effects of [8-Arg]vasopressin (AVP) in regulation of renal water excretion are initiated by stimulation of adenylate cyclase (AdC) coupled with V2 receptors. We explored whether the AVP-sensitive AdC is present in both collecting tubules and the thick ascending limb of Henle's loop of human and canine kidney. In cortical collecting tubule (CCT) and medullary collecting tubules (MCT) of human kidney, AdC was markedly stimulated by AVP [maximum change from basal level (delta), +2700%] and the the nonhormonal stimulatory agent forskolin (delta, +2000%). In human CCT, the effects of both compounds were synergistic. In contrast, AVP had no effect on AdC in either the medullary (MAL) or cortical (CAL) segment of the thick ascending limb of Henle's loop of human kidney; AVP also did not stimulate AdC in CAL or MAL in the presence of forskolin. Similar to that in the human kidney, in the canine kidney, AdC in CCT and MCT was markedly stimulated by AVP and forskolin (delta, +1000%), but AVP had no effect on AdC in CAL and MAL of the canine kidney. In intact tubules dissected from dog kidney and incubated in vitro, AVP markedly increased cAMP accumulation in MCT. AVP also elicited a small but detectable increase in cAMP accumulation in MAL. From these observations, we conclude that AVP-sensitive AdC is well developed in collecting tubules, but that AVP-sensitive AdC is absent in MAL and CAL of human kidney. Likewise, in canine nephron, the AVP-sensitive AdC of MAL and CAL is rudimentary or very labile. These findings suggest that the unresponsiveness of the AdC-cAMP system to AVP in segments of the thick ascending limb of Henle's loop may be a factor that accounts for a relatively low maximum osmotic concentration of urine which can be achieved by human or canine kidneys.
[8-精氨酸]血管加压素（AVP）调节肾脏水排泄的主要肾小管效应是通过刺激与V2受体偶联的腺苷酸环化酶（AdC）启动的。我们探究了AVP敏感的AdC是否存在于人和犬肾的集合小管以及亨氏袢升支粗段中。在人肾的皮质集合小管（CCT）和髓质集合小管（MCT）中，AVP能显著刺激AdC（相对于基础水平的最大变化量（δ），+2700%），非激素刺激剂福斯可林也能显著刺激AdC（δ，+2000%）。在人CCT中，这两种化合物的作用具有协同性。相比之下，AVP对人肾亨氏袢升支粗段的髓质（MAL）或皮质（CAL）段的AdC均无影响；在存在福斯可林的情况下，AVP也不刺激CAL或MAL中的AdC。与人肾相似，在犬肾中，CCT和MCT中的AdC受到AVP和福斯可林的显著刺激（δ，+1000%），但AVP对犬肾的CAL和MAL中的AdC无影响。在从犬肾分离并体外孵育的完整小管中，AVP显著增加了MCT中的cAMP积累。AVP也使MAL中的cAMP积累有小幅但可检测到的增加。基于这些观察结果，我们得出结论，AVP敏感的AdC在集合小管中发育良好，但在人肾的MAL和CAL中不存在AVP敏感的AdC。同样，在犬肾单位中，MAL和CAL的AVP敏感的AdC发育不全或非常不稳定。这些发现表明，亨氏袢升支粗段各节段中AdC - cAMP系统对AVP无反应可能是导致人或犬肾所能达到的尿液最大渗透浓度相对较低的一个因素。
