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Angiotensin IV AT4-receptor system in the rat kidney.

机译:大鼠肾脏中的血管紧张素IV AT4-受体系统。

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摘要

Angiotensin IV, [[des-Asp1,Arg2]ANG II or ANG-(3-8)], has been shown to preferentially bind to a novel angiotensin binding site (AT4 receptor). The cellular location and function of this receptor in the rat kidney is unknown. Autoradiography localized AT4 receptors to the cell body and apical membrane of convoluted and straight proximal tubules in the cortex and outer stripe of the outer medulla. ANG IV (0.1 pM-1 microM) elicited a concentration-dependent decrease in transcellular Na+ transport (as measured by proximal tubule O2 consumption rates) in fresh suspensions of control or nystatin-stimulated (bypasses rate-limiting step of apical Na+ entry) rat proximal tubules. The inhibitory effect of 1 pM ANG IV was unaltered by either 1 microM losartan (AT1-receptor antagonist) or 1 microM PD-123319 (AT2-receptor antagonist) and yet was abolished by 1 microM divalinal-ANG IV (AT4-receptor antagonist) or ouabain pretreatment. These results demonstrate that the kidney AT4-receptor system is localized to the proximal tubule and suggests that one potential biological role of this system is in the regulation of Na+ transport by inhibiting a ouabain-sensitive component of Na(+)-K(+)-adenosinetriphosphatase activity in the rat.
机译:血管紧张素IV,[[des-Asp1,Arg2] ANG II或ANG-(3-8)]已显示优先结合新的血管紧张素结合位点(AT4受体)。该受体在大鼠肾脏中的细胞定位和功能尚不清楚。放射自显影将AT4受体定位于皮质和外延髓的皮层和外条纹中的回旋和笔直的近端小管的细胞体和顶膜。 ANG IV(0.1 pM-1 microM)引起对照或制霉菌素刺激(绕过顶端Na +进入的限速步骤)大鼠新鲜悬液中跨细胞Na +转运的浓度依赖性降低(通过近端小管O2消耗率测量)近端小管。 1 pM ANG IV的抑制作用不会因1 microM氯沙坦(AT1受体拮抗剂)或1 microM PD-123319(AT2受体拮抗剂)而改变,但已被1 microM divalinal-ANG IV(AT4受体拮抗剂)取消。或哇巴因预处理。这些结果表明,肾脏AT4-受体系统位于近端肾小管,提示该系统的一种潜在生物学作用是通过抑制哇巴因敏感的Na(+)-K(+)成分来调节Na +的转运。 -大鼠腺苷三磷酸酶活性。

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