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首页> 外文期刊>American Journal of Physiology >ERK mediates inhibition of Na(+)/H(+) exchange and HCO(3)(-) absorption by nerve growth factor in MTAL.
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ERK mediates inhibition of Na(+)/H(+) exchange and HCO(3)(-) absorption by nerve growth factor in MTAL.

机译：ERK介导神经生长因子在MTAL中抑制Na（+）/ H（+）交换和HCO（3）（-）的吸收。

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摘要

Mitogen-activated protein (MAP) kinases mediate a variety of critical cellular events, but their role in the regulation of epithelial transport is largely undefined. Recently, we demonstrated that nerve growth factor (NGF) inhibits HCO(3)(-) absorption in the rat medullary thick ascending limb (MTAL) through an unusual mechanism: 1) NGF inhibits basolateral membrane Na(+)/H(+) exchange activity, an effect opposite to the stimulation of Na(+)/H(+) exchange by growth factors in other cells; and 2) inhibition of basolateral Na(+)/H(+) exchange results secondarily in inhibition of apical Na(+)/H(+) exchange, thereby inhibiting HCO(3)(-) absorption. In this study, we examined the role of MAP kinases in mediating inhibition by NGF. In tissue strips from the inner stripe of the outer medulla and in microdissected MTALs, NGF increased extracellular signal-regulated kinase (ERK) activity twofold but had no effect on c-Jun NH(2)-terminal kinase (JNK) or p38 MAP kinase activity. The selective MAP kinase kinase (MEK1/2) inhibitors U0126 and PD-98059 abolished the NGF-induced ERK activation and largely eliminated (> or = 60%) the effects of NGF to inhibit basolateral Na(+)/H(+) exchange activity and transepithelial HCO absorption in perfused MTALs. The MEK1/2 inhibitors did not affect inhibition of HCO(3)(-) absorption by bath ethylisopropyl amiloride, indicating that ERK activation is not involved in mediating interaction between the basolateral and apical Na(+)/H(+) exchangers. These results demonstrate that NGF inhibits basolateral Na(+)/H(+) exchange activity and HCO(3)(-) absorption in the MTAL through activation of the ERK signaling pathway. These findings identify a novel action of ERK to inhibit Na(+)/H(+) exchange activity and establish a role for MAP kinase pathways in the acute regulation of Na(+)/H(+) exchange activity and transepithelial acid secretion in renal tubules.
机译：丝裂原激活的蛋白（MAP）激酶介导各种关键的细胞事件，但它们在上皮运输调节中的作用在很大程度上尚不清楚。最近，我们证明了神经生长因子（NGF）通过异常机制抑制了大鼠髓质厚上升肢（MTAL）中HCO（3）（-）的吸收：1）NGF抑制了基底外侧膜Na（+）/ H（+）交换活性，与其他细胞中生长因子刺激Na（+）/ H（+）交换相反的作用; 2）抑制基底外侧Na（+）/ H（+）交换，其次是抑制顶端Na（+）/ H（+）交换，从而抑制HCO（3）（-）的吸收。在这项研究中，我们检查了MAP激酶在NGF介导的抑制作用中的作用。在外部髓质的内部条带和显微解剖的MTALs中，NGF使细胞外信号调节激酶（ERK）活性增加两倍，但对c-Jun NH（2）-末端激酶（JNK）或p38 MAP激酶没有影响活动。选择性MAP激酶激酶（MEK1 / 2）抑制剂U0126和PD-98059废除了NGF诱导的ERK活化，并很大程度上消除了（>或= 60％）NGF抑制基底外侧Na（+）/ H（+）交换的作用灌注的MTALs中的活性和经上皮HCO吸收。 MEK1 / 2抑制剂不会影响抑制HCO（3）（-）吸收的浴乙基异丙基阿米洛利，表明ERK激活不参与介导基底外侧和顶端Na（+）/ H（+）交换子之间的相互作用。这些结果表明，NGF通过激活ERK信号通路抑制MTAL中的基底外侧Na（+）/ H（+）交换活性和HCO（3）（-）吸收。这些发现确定了ERK抑制Na（+）/ H（+）交换活性的新作用，并确定了MAP激酶途径在急性调节Na（+）/ H（+）交换活性和跨膜上皮酸分泌中的作用。肾小管。

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