Lysophosphatidic acid‐LPA1 receptor–Rho–Rho kinase‐induced up‐regulation of Nav1.7 sodium channel mRNA and protein in adrenal chromaffin cells: enhancement of 22Na+ influx, 45Ca2+ influx and catecholamine secretion
Lysophosphatidic acid‐LPA1 receptor–Rho–Rho kinase‐induced up‐regulation of Nav1.7 sodium channel mRNA and protein in adrenal chromaffin cells: enhancement of 22Na+ influx, 45Ca2+ influx and catecholamine secretion
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DOI：
10.1111/j.1471-4159.2007.05143.x
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发表时间：
2008-04
影响因子：
4.7
通讯作者：
Toyoaki Maruta;T. Yanagita;Kiyotaka Matsuo;Y. Uezono;Shinya Satoh;Takayuki Nemoto;Norie Yoshikawa;Hideyuki Kobayashi;M. Takasaki;A. Wada
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文献类型：
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作者：
Toyoaki Maruta;T. Yanagita;Kiyotaka Matsuo;Y. Uezono;Shinya Satoh;Takayuki Nemoto;Norie Yoshikawa;Hideyuki Kobayashi;M. Takasaki;A. Wada
在培养的牛肾上腺染色质细胞中，溶血磷脂酸（LPA）慢性（≥24 h）处理使veratridine诱导的22Na+内流通过Nav1.7增加了约22% (EC50 = 1 nmol/L)，而尼古丁诱导的22Na+内流通过尼古丁受体相关通道没有改变。LPA通过电压依赖性钙通道和儿茶酚胺分泌增强了veratridine（而不是尼古丁）诱导的45Ca2+内流。LPA使veratliine对22Na+内流的浓度-响应曲线向上移动，但没有改变veratliine的EC50。短斑蝶毒素- 3在未处理和LPA处理的细胞中变张力增强了两倍的veratridine诱导的22Na+内流。全细胞膜片钳分析显示，LPA （100 nmol/L，持续36 h）处理的细胞Na+电流峰值幅度增加39%；然而，在未处理和LPA处理的细胞之间，I-V曲线和稳态失活/激活曲线具有可比性。LPA处理（≥24 h）使细胞表面[3H]石蜡毒素结合增加约28%，而Kd值没有改变；环己亚胺、放线菌素D或Ki16425、焦磷酸二辛基甘油8:0 （LPA1和LPA3受体的两种抑制剂）或肉毒杆菌毒素C3 （Rho抑制剂）、Y27632 （Rho激酶抑制剂）可阻止LPA1受体在肾上腺染色质细胞中的表达，这与LPA1受体在肾上腺染色质细胞中的表达一致。LPA使Nav1.7 mRNA水平升高约37%。因此，LPA-LPA1受体- Rho/Rho激酶通路上调了细胞表面Nav1.7和Nav1.7 mRNA水平，增强了veratridine诱导的Ca2+内流和儿茶酚胺分泌。
In cultured bovine adrenal chromaffin cells, chronic (≥ 24 h) treatment with lysophosphatidic acid (LPA) augmented veratridine‐induced 22Na+ influx via Nav1.7 by ∼22% (EC50 = 1 nmol/L), without changing nicotine‐induced 22Na+ influx via nicotinic receptor‐associated channel. LPA enhanced veratridine (but not nicotine)‐induced 45Ca2+ influx via voltage‐dependent calcium channel and catecholamine secretion. LPA shifted concentration–response curve of veratridine for 22Na+ influx upward, without altering the EC50 of veratridine. Ptychodiscus brevis toxin‐3 allosterically enhanced veratridine‐induced 22Na+ influx by twofold in non‐treated and LPA‐treated cells. Whole‐cell patch‐clamp analysis showed that peak Na+ current amplitude was greater by 39% in LPA (100 nmol/L for 36 h)‐treated cells; however, I–V curve and steady‐state inactivation/activation curves were comparable between non‐treated and LPA‐treated cells. LPA treatment (≥ 24 h) increased cell surface [3H]saxitoxin binding by ∼28%, without altering the Kd value; the increase was prevented by cycloheximide, actinomycin D, or Ki16425, dioctylglycerol pyrophosphate 8:0 (two inhibitors of LPA1 and LPA3 receptors), or botulinum toxin C3 (Rho inhibitor), Y27632 (Rho kinase inhibitor), consistent with LPA1 receptor expression in adrenal chromaffin cells. LPA raised Nav1.7 mRNA level by ∼37%. Thus, LPA–LPA1 receptor–Rho/Rho kinase pathway up‐regulated cell surface Nav1.7 and Nav1.7 mRNA levels, enhancing veratridine‐induced Ca2+ influx and catecholamine secretion.