Yano Yuristella, Rodrígues Adilson C, de Bragança Ana C, Andrade Lucia C, Magaldi Antonio J
Laboratório de Pesquisa Básica-LIM 12, Hospital das Clínicas da Faculdade de Medicina-Nefrologia, Universidade de São Paulo, Av Dr Arnaldo, 455, São Paulo, SP, 01246-903, Brasil.
Pflugers Arch. 2008 Sep;456(6):1229-37. doi: 10.1007/s00424-008-0478-5. Epub 2008 May 1.
It is well-known that glucagon increases fractional excretion of urea in rats after a protein intravenous infusion. This effect was investigated by using: (a) in vitro microperfusion technique to measure [(14)C]-urea permeability (Pu x 10(-5)cm/s) in inner medullary collecting ducts (IMCD) from normal rats in the presence of 10(-7)M of glucagon and in the absence of vasopressin and (b) immunoblot techniques to determine urea transporter expression in tubule suspension incubated with the same glucagon concentration. Seven groups of IMCDs (n = 47) were studied. Our results revealed that: (a) glucagon decreased urea reabsorption dose-dependently; (b) the glucagon antagonist des-His(1)-[Glu(9)], blocked the glucagon action but not vasopressin action; (c) the phorbol myristate acetate, decreased urea reabsorption but (d) staurosporin, restored its effect; e) staurosporin decreased glucagon action, and finally, (f) glucagon decreased UT-A1 expression. We can conclude that glucagon reduces UT-A1 expression via a glucagon receptor by stimulating PKC.
众所周知，在给大鼠静脉输注蛋白质后，胰高血糖素会增加尿素的排泄分数。通过以下方法对这种作用进行了研究：(a) 使用体外微灌注技术，在不存在血管加压素的情况下，于10(-7)M胰高血糖素存在时，测量正常大鼠髓质内集合管（IMCD）中的[(14)C] - 尿素通透性（Pu×10(-5)cm/s）；(b) 使用免疫印迹技术，确定在相同胰高血糖素浓度下孵育的肾小管悬浮液中尿素转运蛋白的表达。研究了七组IMCD（n = 47）。我们的结果显示：(a)胰高血糖素剂量依赖性地降低尿素重吸收；(b)胰高血糖素拮抗剂des-His(1)-[Glu(9)]可阻断胰高血糖素的作用，但不阻断血管加压素的作用；(c)佛波醇肉豆蔻酸酯降低尿素重吸收，但(d)星形孢菌素可恢复其作用；(e)星形孢菌素降低胰高血糖素的作用，最后(f)胰高血糖素降低UT-A1表达。我们可以得出结论，胰高血糖素通过刺激蛋白激酶C，经由胰高血糖素受体降低UT-A1表达。
