Alfaidy N, Blot-Chabaud M, Bonvalet J P, Farman N
INSERM U246, Institut Fédératif de Recherches Cellules Epithéliales, Faculté de Médecine X. Bichat, Paris, France.
J Clin Invest. 1997 Nov 15;100(10):2437-42. doi: 10.1172/JCI119785.
Arginine vasopressin (AVP) and corticosteroid hormones are involved in sodium reabsorption regulation in the renal collecting duct. Synergy between AVP and aldosterone has been well documented, although its mechanism remains unclear. Both aldosterone and glucocorticoid hormones bind to the mineralocorticoid receptor (MR), and mineralocorticoid selectivity depends on the MR-protecting enzyme 11 beta hydroxysteroid deshydrogenase (11-HSD), which metabolizes glucocorticoids into derivatives with low affinity for MR. We have investigated whether the activity of 11-HSD could be influenced by AVP and corticosteroid hormones. This study shows that in isolated rat renal collecting ducts, AVP increases 11-HSD catalytic activity. This effect is maximal at 10(-8) M AVP (a concentration clearly above the normal physiological range of AVP concentrations) and involves the V2 receptor pathway, while activation of protein kinase C or changes in intracellular calcium are ineffective. The stimulatory effect of AVP on 11-HSD is largely reduced after adrenalectomy, and is selectively restored by infusion of aldosterone, not glucocorticoids. We conclude that this synergy between AVP and aldosterone in controlling the activity of 11-HSD is likely to play a pivotal role in resetting mineralocorticoid selectivity, and hence sodium reabsorption capacities of the renal collecting duct.
精氨酸加压素（AVP）和皮质类固醇激素参与肾集合管中钠重吸收的调节。AVP与醛固酮之间的协同作用已有充分记录，但其机制仍不清楚。醛固酮和糖皮质激素均与盐皮质激素受体（MR）结合，而盐皮质激素的选择性取决于MR保护酶11β-羟类固醇脱氢酶（11-HSD），该酶将糖皮质激素代谢为对MR亲和力低的衍生物。我们研究了11-HSD的活性是否会受到AVP和皮质类固醇激素的影响。本研究表明，在离体大鼠肾集合管中，AVP可增加11-HSD的催化活性。这种效应在AVP浓度为10^(-8) M时最大（该浓度明显高于AVP浓度的正常生理范围），且涉及V2受体途径，而蛋白激酶C的激活或细胞内钙的变化则无效。肾上腺切除术后，AVP对11-HSD的刺激作用大大降低，通过输注醛固酮而非糖皮质激素可选择性恢复。我们得出结论，AVP与醛固酮在控制11-HSD活性方面的这种协同作用可能在重置盐皮质激素选择性以及肾集合管的钠重吸收能力方面起关键作用。
