Ardaillou N, Nivez M P, Schambelan M, Ardaillou R
J Clin Endocrinol Metab. 1983 Dec;57(6):1207-15. doi: 10.1210/jcem-57-6-1207.
A role for hormonal substances and other biochemical messengers in the regulation of the glomerular filtration rate has been inferred from the results of micropuncture studies in the rat and from the demonstration of hormone-responsive adenylate cyclase activity in glomeruli isolated from the renal cortex of rats and rabbits. To investigate whether such hormonal factors may contribute to the regulation of glomerular function in humans, we studied the response of adenylate cyclase activity to the administration of human PTH-(1-34) and prostaglandins (PG) by glomeruli isolated from the renal cortex of four human kidneys. PTH and PGs (PGE2, PGI2, and, to a lesser extent, PGF2 alpha) stimulated human glomerular adenylate cyclase activity. Basal adenylate cyclase activity ranged from 0.2-1.2 nmol 20 min-1 mg-1. For each agonist, the percent increase above basal values (at the maximum concentration tested) and the concentration of the agonist that elicited 50% of the maximum stimulation (ED50) were as follows: for PTH 300-460% (10,000 mIU/ml); ED50, 100-550 mIU/ml; for PGE2, 160-380% (10 microM); ED50, 0.4-1.6 microM; and for PGI2, 180-650% (10 microM); ED50, 0.09-0.46 microM. The synthetic guanylnucleotide 5'-guanylylimidodiphosphate [Gpp(NH)p] potentiated the effect of PTH and PGI2, since the combined effects were greater than the sums of the effects of the individual agonists, and there was a significant interaction between Gpp(NH)p and PTH or PGI2, as indicated by three-factor analysis of variance. Additivity, but not potentiation, was observed for PGE2. The effects of PTH plus PGE2 or PGI2 were also additive, a finding that suggests that PTH and PGs are not linked to the same pool of adenylate cyclase. In contrast, the combination of PGE2 and PGI2 resulted in a significantly lower effect than the sum of their individual effects, a finding indicating that these PGs share in part a common pool of adenylate cyclase. Demonstration of PTH- and PG-dependent adenylate cyclase activity in human isolated glomeruli suggests a role for these agonists in the regulation of the glomerular filtration rate in man.
从对大鼠的微穿刺研究结果以及在从大鼠和兔子肾皮质分离出的肾小球中证明的激素反应性腺苷酸环化酶活性，可推断出激素物质和其他生化信使在肾小球滤过率调节中的作用。为了研究此类激素因素是否可能参与人类肾小球功能的调节，我们研究了从四颗人肾的肾皮质分离出的肾小球对人甲状旁腺激素（1 - 34）[PTH - (1 - 34)]和前列腺素（PG）给药的腺苷酸环化酶活性反应。PTH和PGs（前列腺素E2 [PGE2]、前列环素[PGI2]以及程度稍轻的前列腺素F2α [PGF2α]）刺激了人肾小球腺苷酸环化酶活性。基础腺苷酸环化酶活性范围为0.2 - 1.2 nmol·20 min⁻¹·mg⁻¹。对于每种激动剂，高于基础值的增加百分比（在测试的最大浓度时）以及引发最大刺激50%的激动剂浓度（半数有效浓度[ED50]）如下：对于PTH为300 - 460%（10,000 mIU/ml）；ED50为100 - 550 mIU/ml；对于PGE2为160 - 380%（10 μM）；ED50为0.4 - 1.6 μM；对于PGI2为180 - 650%（10 μM）；ED50为0.09 - 0.46 μM。合成鸟苷酸5'-鸟苷酰亚胺二磷酸[Gpp(NH)p]增强了PTH和PGI2的作用，因为联合作用大于各个激动剂作用之和，并且通过三因素方差分析表明Gpp(NH)p与PTH或PGI2之间存在显著相互作用。对于PGE2观察到的是相加作用而非增强作用。PTH加PGE2或PGI2的作用也是相加的，这一发现表明PTH和PGs与不同的腺苷酸环化酶池相关联。相反，PGE2和PGI2的组合导致的作用明显低于它们各自作用之和，这一发现表明这些PGs部分共享一个共同的腺苷酸环化酶池。在人分离的肾小球中证明PTH和PG依赖的腺苷酸环化酶活性表明这些激动剂在人类肾小球滤过率调节中起作用。
