Doucet A, Barlet-Bas C, Siaume-Perez S, Khadouri C, Marsy S
Laboratoire de Physiologie Cellulaire, URA 219 Centre National de la Recherche Scientifique, Collège de France, Paris.
Am J Physiol. 1990 Apr;258(4 Pt 2):F812-20. doi: 10.1152/ajprenal.1990.258.4.F812.
Adrenal insufficiency is associated with an impairment of kidney diluting and concentrating ability, defects that may result from alterations of vasopressin-induced adenosine 3',5'-cyclic monophosphate (cAMP) production. The purpose of this study were 1) to localize the sites of decreased vasopressin-stimulated adenylate cyclase (AC) activity along the nephron of adrenalectomized rats; 2) to determine whether the response of AC to other hormones is altered by adrenalectomy; 3) to evaluate whether changes in AC are due to the deficiency in mineralocorticoids and/or glucocorticoids; and 4) to characterize the mechanism of action of corticosteroids on the AC system. Results indicate that adrenalectomy reduced AC stimulation by vasopressin, glucagon, and calcitonin in the thick ascending limb, whereas only the response to vasopressin decreased in the collecting tubule. Glucocorticoid administration curtailed adrenalectomy-induced alterations of AC in the thick ascending limb, whereas that in the collecting tubule was prevented by mineralocorticoids. Adrenalectomy did not alter forskolin-stimulated AC, whereas it decreased responses to aluminum fluoride and cholera toxin. Finally, alterations of fluoride- and cholera toxin-stimulated AC were prevented by glucocorticoid and mineralocorticoid repletion in the thick ascending limb and collecting tubule, respectively.
肾上腺功能不全与肾脏稀释和浓缩能力受损有关，这些缺陷可能是由血管加压素诱导的3',5'-环磷酸腺苷（cAMP）生成改变所致。本研究的目的是：1）确定去肾上腺大鼠肾单位中血管加压素刺激的腺苷酸环化酶（AC）活性降低的部位；2）确定肾上腺切除术是否会改变AC对其他激素的反应；3）评估AC的变化是否归因于盐皮质激素和/或糖皮质激素缺乏；4）描述皮质类固醇对AC系统的作用机制。结果表明，肾上腺切除术降低了血管加压素、胰高血糖素和降钙素对厚升支中AC的刺激，而在集合管中只有对血管加压素的反应降低。给予糖皮质激素可减少肾上腺切除术引起的厚升支中AC的改变，而集合管中的改变则可被盐皮质激素阻止。肾上腺切除术未改变福斯高林刺激的AC，而降低了对氟化铝和霍乱毒素的反应。最后，厚升支和集合管中分别通过补充糖皮质激素和盐皮质激素预防了氟化铝和霍乱毒素刺激的AC的改变。
