血管紧张素 -（1 - 7）通过一种对A779敏感的受体逆转血管紧张素II对近端小管钠钾ATP酶活性的刺激作用。

Angiotensin-(1-7) reverts the stimulatory effect of angiotensin II on the proximal tubule Na(+)-ATPase activity via a A779-sensitive receptor.

作者信息

Lara Lucienne S, Bica Rafael B S, Sena Sílvia L F, Correa Juliana S, Marques-Fernandes Maria F, Lopes Aníbal G, Caruso-Neves Celso

机构信息

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS-Bloco G, 21949-900, RJ, Rio de Janeiro, Brazil.

出版信息

Regul Pept. 2002 Jan 15;103(1):17-22. doi: 10.1016/s0167-0115(01)00322-6.

DOI:10.1016/s0167-0115(01)00322-6

PMID:11738244

Abstract

Recently, we demonstrated that the stimulatory effect of Ang II on the Na(+)-ATPase activity in proximal tubules is reversed, in a dose-dependent manner, by Ang-(1-7) [Biochim. Biophys. Acta 1467 (2000) 189]. In the present paper, we characterized the receptor involved in this phenomenon. The preincubation of the Na(+)-ATPase with 10(-8) M Ang II increases the enzyme activity from 7.50+/-0.02 (control) to 12.40+/-1.50 nmol Pi mg(-1) min(-1) (p<0.05). Addition of 10(-9) M Ang-(1-7) completely reverts this effect returning the ATPase activity to the control level. This effect seems to be specific to Ang-(1-7) since Ang III (10(-12)-10(-8) M) does not modify the stimulation of the renal proximal tubule Na(+)-ATPase activity by Ang II. Saralasin abolishes the Ang-(1-7) effect in a dose-dependent manner being the maximal effect obtained at 10(-11) M. The increase in A779 concentration (from 10(-12) to 10(-7) M), a specific Ang-(1-7) antagonist, also abolishes the Ang-(1-7) effect. On the other hand, PD123319 (10(-8)-10(-6) M), an AT(2) antagonist receptor, and losartan (10(-12)-10(-7) M), an AT(1) antagonist receptor, does not modify the effect of Ang-(1-7). Taken together, these data indicate that Ang-(1-7) reverts the stimulatory effect of Ang II on the Na(+)-ATPase activity in proximal tubule through a A779-sensitive receptor.

摘要

最近，我们证明了血管紧张素II（Ang II）对近端小管中钠钾ATP酶（Na(+)-ATPase）活性的刺激作用，可被血管紧张素-(1-7)（Ang-(1-7)）以剂量依赖的方式逆转[《生物化学与生物物理学报》1467 (2000) 189]。在本文中，我们对参与这一现象的受体进行了特性描述。将Na(+)-ATPase与10(-8) M Ang II预孵育，可使酶活性从7.50±0.02（对照）增加至巧12.40±1.50 nmol Pi mg(-1) min(-1)（p<0.05）。加入10(-9) M Ang-(1-7)可完全逆转这一效应，使ATP酶活性恢复至对照水平。这种效应似乎对Ang-(1-7)具有特异性，因为血管紧张素III（Ang III，10(-12)-10(-8) M）不会改变Ang II对肾近端小管Na(+)-ATPase活性的刺激作用。沙拉新（Saralasin）以剂量依赖的方式消除Ang-(1-7)的作用，在10(-11) M时可获得最大效应。特异性Ang-(1-7)拮抗剂A779浓度的增加（从10(-12)至10(-7) M）也可消除Ang-(1-7)的作用。另一方面，AT(2)拮抗剂受体PD123319（10(-8)-10(-6) M）和AT(1)拮抗剂受体氯沙坦（losartan，10(-12)-10(-7) M）不会改变Ang-(1-7)的作用。综上所述，这些数据表明，Ang-(1-7)通过一种对A779敏感的受体逆转了Ang II对近端小管中Na(+)-ATPase活性的刺激作用。