Prié D, Friedlander G, Coureau C, Vandewalle A, Cassingéna R, Ronco P M
INSERM U251, Faculté de Médecine Xavier Bichat, Paris, France.
Kidney Int. 1995 May;47(5):1310-8. doi: 10.1038/ki.1995.186.
The hormonal responsiveness profile of the cortical collecting duct varies from one species to another. To identify the hormones and agonists that modulate the functions of this tubule segment in the human species, we generated a cell line (HCD) immortalized by SV40 virus. The tubular origin of this cell line was assessed by the expression of collecting duct-specific antigens and the ability of vasopressin to increase by nine-fold cAMP synthesis. Glucagon and adenosine stimulated cAMP synthesis, and atrial natriuretic peptide stimulated cGMP synthesis in a concentration-dependent manner. Bradykinin, adenosine and angiotensin increased intracellular calcium concentration ([Ca2+]i). Because adenosine can regulate tubular functions, we examined its role on glucagon-induced cAMP synthesis. Using adenosine analogs, we demonstrated that HCT cells both expressed adenosine type-2 (A2) receptors which stimulated cAMP production, and adenosine type-1 (A1) receptors linked to [Ca2+]i increase which inhibited glucagon-stimulated cAMP synthesis. The inhibitory effect was abolished by pertussis toxin, and was neither due to [Ca2+]i increase nor to protein kinase C activation, which indicated that some A1 adenosine receptors were directly negatively coupled to adenylyl cyclase. These results suggest that adenosine can modify human cortical collecting duct functions in opposite ways according to the adenosine receptor activated.
皮质集合管的激素反应性模式因物种而异。为了确定调节人类该肾小管节段功能的激素和激动剂，我们构建了一种由SV40病毒永生化的细胞系（HCD）。通过集合管特异性抗原的表达以及血管加压素使环磷酸腺苷（cAMP）合成增加九倍的能力来评估该细胞系的肾小管起源。胰高血糖素和腺苷以浓度依赖的方式刺激cAMP合成，心房利钠肽刺激环磷酸鸟苷（cGMP）合成。缓激肽、腺苷和血管紧张素增加细胞内钙浓度（[Ca2+]i）。由于腺苷可调节肾小管功能，我们研究了其对胰高血糖素诱导的cAMP合成的作用。使用腺苷类似物，我们证明HCT细胞既表达刺激cAMP产生的2型腺苷（A2）受体，也表达与[Ca2+]i增加相关的1型腺苷（A1）受体，后者抑制胰高血糖素刺激的cAMP合成。百日咳毒素消除了这种抑制作用，且该抑制作用既不是由于[Ca2+]i增加也不是由于蛋白激酶C激活所致，这表明一些A1腺苷受体直接与腺苷酸环化酶负偶联。这些结果表明，根据激活的腺苷受体不同，腺苷可以以相反的方式调节人类皮质集合管的功能。
