Kittikulsuth Wararat, Stuart Deborah, Van Hoek Alfred N, Kohan Donald E
Division of Nephrology, University of Utah Health Sciences Center Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT.
Division of Nephrology, University of Utah Health Sciences Center Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT
Physiol Rep. 2015 Mar;3(3). doi: 10.14814/phy2.12316.
Adenylyl cyclase (AC)-stimulated cAMP plays a key role in modulating transport and channel activity along the nephron. However, the role of individual adenylyl cyclase isoforms in such regulation is largely unknown. Since adenylyl cyclase 3 (AC3) is expressed throughout nephron, we investigated its role in the physiologic regulation of renal Na(+) and water transport. Mice were generated with inducible nephron knockout of AC3 (AC3 KO) by breeding mice with loxP-flanked critical exons in the Adcy3 gene with mice expressing Pax8-rtTA and LC-1 transgenes. After doxycycline treatment at 1 month of age, nephron AC3 KO mice had 100% Adcy3 gene recombination in all renal tubule segments, but not in glomeruli. Sodium intake, urinary Na(+) excretion, glomerular filtration rate, and blood pressure were similar between nephron KO mice and the controls during normal, high, and low Na(+) diets. Plasma renin concentration was not different between the two groups during varied Na(+) intake. Moreover, there were no differences in urine volume and urine osmolality between the two genotypes during normal or restricted water intake. In conclusion, these data suggested that AC3 is not involved in the physiological regulation of nephron Na(+) and water handling.
腺苷酸环化酶（AC）刺激产生的环磷酸腺苷（cAMP）在调节肾单位的转运和通道活性中起关键作用。然而，单个腺苷酸环化酶同工型在这种调节中的作用很大程度上尚不清楚。由于腺苷酸环化酶3（AC3）在整个肾单位中均有表达，我们研究了其在肾脏钠（Na⁺）和水转运的生理调节中的作用。通过将在Adcy3基因中带有loxP侧翼关键外显子的小鼠与表达Pax8-rtTA和LC-1转基因的小鼠杂交，生成了可诱导肾单位敲除AC3的小鼠（AC3 KO）。在1月龄给予强力霉素处理后，肾单位AC3 KO小鼠在所有肾小管节段中Adcy3基因重组率达100%，但在肾小球中未出现。在正常、高钠和低钠饮食期间，肾单位敲除小鼠与对照组之间的钠摄入量、尿钠（Na⁺）排泄、肾小球滤过率和血压相似。在不同钠（Na⁺）摄入量时，两组之间的血浆肾素浓度无差异。此外，在正常或限水摄入期间，两种基因型之间的尿量和尿渗透压也没有差异。总之，这些数据表明AC3不参与肾单位钠（Na⁺）和水代谢的生理调节。
