Jensen R E, Berndt W O
Department of Pharmacology, University of Nebraska College of Medicine, Omaha.
J Pharmacol Exp Ther. 1988 Feb;244(2):543-9.
The effect of exogenous l-norepinephrine (NE) and l-epinephrine (EP) on transmembrane transport of p-aminohippurate (PAH) was studied in rat proximal tubular basolateral membrane vesicles. A gradient of 50 mM Na+ (out greater than in) and preloading of vesicles with unlabeled PAH were utilized to promote the influx of [3H]PAH into the vesicles. At final concentrations of 1 microM, NE and EP each produced significant elevations in vesicle uptake of [3H]PAH. The enhancement of PAH transport by NE or EP was inhibited by either phentolamine (100 microM) or yohimbine (100 microM). Prazosin (100 microM) or atenolol (100 microM) were unable to inhibit the response to NE. Similarly, prazosin or propranolol (100 microM) were unable to inhibit the response to EP. Clonidine (1 microM) also produced a significant elevation of PAH uptake, an effect inhibited by both phentolamine and yohimbine. Basolateral Na+-K+-adenosine triphosphatase activity also was increased significantly by either NE or EP (1 microM). Both agonists produced significant elevations of PAH uptake into vesicles preloaded with ATP. However, in the absence of NE or EP, PAH uptake into ATP-loaded vesicles was not significantly greater than into control vesicles. It was concluded that NE and EP enhance Na+-coupled PAH transport and that this effect may be mediated by alpha-2 adrenergic receptors. Activation of Na+-K+-adenosine triphosphatase is a possible mechanism whereby adrenergic agonists may exert effects on Na+-coupled transport across the basolateral membrane.
在大鼠近端肾小管基底外侧膜囊泡中研究了外源性左旋去甲肾上腺素（NE）和左旋肾上腺素（EP）对对氨基马尿酸（PAH）跨膜转运的影响。利用50 mM Na⁺梯度（胞外大于胞内）以及用未标记的PAH预加载囊泡来促进[³H]PAH流入囊泡。在最终浓度为1 μM时，NE和EP均使[³H]PAH的囊泡摄取量显著升高。NE或EP对PAH转运的增强作用被酚妥拉明（100 μM）或育亨宾（100 μM）抑制。哌唑嗪（100 μM）或阿替洛尔（100 μM）无法抑制对NE的反应。同样，哌唑嗪或普萘洛尔（100 μM）无法抑制对EP的反应。可乐定（1 μM）也使PAH摄取量显著升高，该作用被酚妥拉明和育亨宾均抑制。基底外侧Na⁺-K⁺-三磷酸腺苷酶活性也被NE或EP（1 μM）显著增加。两种激动剂均使预加载ATP的囊泡中PAH摄取量显著升高。然而，在不存在NE或EP的情况下，加载ATP的囊泡中PAH摄取量并不显著高于对照囊泡。得出的结论是，NE和EP增强Na⁺偶联的PAH转运，且该作用可能由α-2肾上腺素能受体介导。Na⁺-K⁺-三磷酸腺苷酶的激活是肾上腺素能激动剂可能对跨基底外侧膜的Na⁺偶联转运发挥作用的一种可能机制。
