Alpha 2 adrenergic agonists stimulate Na+-H+ antiport activity in the rabbit renal proximal tubule.
Alpha 2 adrenergic agonists stimulate Na+-H+ antiport activity in the rabbit renal proximal tubule.
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α 2 肾上腺素能激动剂刺激兔肾近曲小管中的 Na -H 反向转运活性。
DOI：
10.1172/jci113268
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Insel,PA
中科院分区：
文献类型：
--
作者：
Nord,EP;Howard,MJ;Hafezi,A;Moradeshagi,P;Vaystub,S;Insel,PA
在新鲜分离的兔肾近端肾小管细胞悬浮液的制备中研究了肾上腺素能药物在增加近端肾小管盐和水通量中的作用。去甲肾上腺素 (NE, 10(-5) M) 使钠流入量 (JNa) 增加至对照值以上 60 +/- 5%。 α 肾上腺素能拮抗剂酚妥拉明 (10(-5) M) 可抑制 NE 诱导的 JNa 增强 90 +/- 2%，而 β 肾上腺素能拮抗剂普萘洛尔则具有最小的抑制作用 (10 +/- 2%)。进一步定义了α肾上腺素能亚型。育亨宾(10(-5)M)是一种α2肾上腺素能拮抗剂，但不是哌唑嗪(10(-5)M)，一种α1肾上腺素能拮抗剂，完全阻断NE诱导的JNa增加。可乐定（一种部分 α2 肾上腺素能激动剂）使 JNa 增加 58 +/- 2%，与使用 NE (10(-5) M) 观察到的结果相当。育亨宾（而非哌唑嗪）抑制可乐定诱导的 JNa 增加，证实 α2 肾上腺素受体参与其中。其他 α2 肾上腺素能药物，尤其是对氨基可乐定和 α-甲基-去甲肾上腺素，也能导致 JNa 类似的增加。可乐定诱导的 JNa 增加可以被阿米洛利类似物乙基异丙基阿米洛利 (EIPA, 10(-5) M) 完全阻断。 EIPA 阻断的转运途径部分被 Li 和顺式 H+ 抑制，但被反式 H+ 刺激，这与 Na+-H+ 反向转运一致。使用[3H]哌唑嗪（α1 肾上腺素能拮抗剂）和[3H]rauwolscine（α2 肾上腺素能拮抗剂）进行放射性配体结合研究，以补充通量研究。 [3H]哌唑嗪与细胞的结合可以忽略不计。相比之下，[3H]rauwolscine 显示出与单一类别位点的饱和结合，Bmax 1678 +/- 143 个结合位点/细胞，KD 5.4 +/- 1.4 nM。总之，在分离的兔肾近端肾小管细胞制剂中，α2肾上腺素受体是α肾上腺素受体的主要表达，并且在缺乏有机Na+共转运溶质的情况下，α2肾上腺素激动剂通过刺激刷状缘膜Na+-H+交换途径来增强22Na流入细胞。
The role of adrenergic agents in augmenting proximal tubular salt and water flux, was studied in a preparation of freshly isolated rabbit renal proximal tubular cells in suspension. Norepinephrine (NE, 10(-5) M) increased sodium influx (JNa) 60 +/- 5% above control value. The alpha adrenergic antagonist, phentolamine (10(-5) M), inhibited the NE-induced enhanced JNa by 90 +/- 2%, while the beta adrenergic antagonist, propranolol, had a minimal inhibitory effect (10 +/- 2%). The alpha adrenergic subtype was further defined. Yohimbine (10(-5) M), an alpha2 adrenergic antagonist but not prazosin (10(-5) M), an alpha1 adrenergic antagonist completely blocked the NE induced increase in JNa. Clonidine, a partial alpha2 adrenergic agonist, increased JNa by 58 +/- 2% comparable to that observed with NE (10(-5) M). Yohimbine, but not prazosin, inhibited the clonidine-induced increase in JNa, confirming that alpha2 adrenergic receptors were involved. Additional alpha2 adrenergic agents, notably p-amino clonidine and alpha-methyl-norepinephrine, imparted a similar increase in JNa. The clonidine-induced increase in JNa could be completely blocked by the amiloride analogue, ethylisopropyl amiloride (EIPA, 10(-5) M). The transport pathway blocked by EIPA was partially inhibited by Li and cis H+, but stimulated by trans H+, consistent with Na+-H+ antiport. Radioligand binding studies using [3H]prazosin (alpha1 adrenergic antagonist) and [3H]rauwolscine (alpha2 adrenergic antagonist) were performed to complement the flux studies. Binding of [3H]prazosin to the cells was negligible. In contrast, [3H]rauwolscine showed saturable binding to a single class of sites, with Bmax 1678 +/- 143 binding sites/cell and KD 5.4 +/- 1.4 nM. In summary, in the isolated rabbit renal proximal tubular cell preparation, alpha2 adrenergic receptors are the predominant expression of alpha adreno-receptors, and in the absence of organic Na+-cotransported solutes, alpha2 adrenergic agonists enhance 22Na influx into the cell by stimulating the brush border membrane Na+-H+ exchange pathway.Images