Carrithers S L, Taylor B, Cai W Y, Johnson B R, Ott C E, Greenberg R N, Jackson B A
Division of Infectious Diseases, University of Kentucky and Lexington Veterans Affairs Medical Center, Research Service 151-CDD, 1101 VA Drive, VAMC-D309, 40506, Lexington, KY, USA.
Regul Pept. 2000 Nov 24;95(1-3):65-74. doi: 10.1016/s0167-0115(00)00139-7.
Guanylin (GN) and uroguanylin (UGN) are two recently identified peptides that have been shown to affect water and electrolyte transport in both the intestine and the kidney. Mechanistically, the effects of both peptides are thought to be mediated by intracellular cGMP which results from ligand binding to a plasma membrane guanylyl cyclase-C (GC-C) receptor. To date, the specific intrarenal site(s) of GN and UGN action have not been established. To begin to address this issue, the present studies utilized semi-quantitative RT-PCR to assess the distribution of GC-C mRNA in specific microdissected segments of the rat nephron. GC-C mRNA expression was highest in the cortical collecting tubule, followed by the proximal convoluted tubule, medullary thick ascending limb and collecting tubule, and thin limbs of Henle's loop. Expression levels were significantly lower in all other segments tested, including the glomerulus. The renal tubular expression pattern for cGMP-dependent protein kinase II (cGK-II) mRNA, which is activated in response to GN/UGN-dependent cGMP accumulation, was similar to that for GC-C. Notably, both GN and UGN mRNAs were also expressed along the nephron. The highest levels of expression for both peptides were detected in the medullary collecting tubule. Lower, but comparable levels of GN and UGN expression also occurred in the cortical collecting tubule, cortical and medullary thick ascending limb, and thin limbs of Henles loop. In the proximal convoluted tubule, GN mRNA expression was also quite high, while UGN mRNA was almost undetectable. The presence of renal GC-C and cGK-II in the kidney are consistent with a proposed endocrine function for GN and UGN. In addition however, the present data suggest that intrarenally synthesized GN and UGN may also contribute to the regulation of renal tubular transport.
鸟苷林（GN）和尿鸟苷林（UGN）是最近发现的两种肽，已证明它们会影响肠道和肾脏中的水和电解质转运。从机制上讲，这两种肽的作用被认为是由细胞内cGMP介导的，cGMP是配体与质膜鸟苷酸环化酶-C（GC-C）受体结合的结果。迄今为止，GN和UGN作用的具体肾内位点尚未确定。为了开始解决这个问题，本研究利用半定量逆转录聚合酶链反应（RT-PCR）来评估大鼠肾单位特定显微切割节段中GC-C mRNA的分布。GC-C mRNA表达在皮质集合管中最高，其次是近端曲管、髓质厚升支和集合管以及亨利袢细段。在所有其他测试节段（包括肾小球）中，表达水平明显较低。cGMP依赖性蛋白激酶II（cGK-II）mRNA的肾小管表达模式与GC-C相似，cGK-II mRNA会因GN/UGN依赖性cGMP积累而被激活。值得注意的是，GN和UGN mRNA也沿肾单位表达。在髓质集合管中检测到这两种肽的最高表达水平。在皮质集合管、皮质和髓质厚升支以及亨利袢细段中，GN和UGN的表达水平较低但相当。在近端曲管中，GN mRNA表达也相当高，而UGN mRNA几乎检测不到。肾脏中存在肾GC-C和cGK-II与GN和UGN的拟议内分泌功能一致。然而，此外，目前的数据表明肾内合成的GN和UGN也可能有助于肾小管转运的调节。
