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肾大部切除大鼠残余肾中肾上腺髓质素及其受体复合物:降钙素受体样受体和受体活性修饰蛋白-3表达降低

Adrenomedullin and its receptor complexes in remnant kidneys of rats with renal mass ablation: decreased expression of calcitonin receptor-like receptor and receptor-activity modifying protein-3.

作者信息

Totsune K, Takahashi K, Mackenzie H S, Arihara Z, Satoh F, Sone M, Murakami O, Ito S, Brenner B M, Mouri T

机构信息

Second Department of Internal Medicine, Tohoku University School of Medicine, 980-8574, Sendai, Miyagi, Japan.

出版信息

Peptides. 2001 Nov;22(11):1933-7. doi: 10.1016/s0196-9781(01)00526-5.

Abstract

Adrenomedullin (AM) has vasodilator and diuretic actions, similarly to natriuretic peptides. AM receptor complexes are composed of calcitonin receptor-like receptor (CRLR) and receptor-activity modifying protein-2 (RAMP2), or CRLR and RAMP3. We aimed to know whether gene expression of AM and AM receptor complexes are regulated in kidneys under pathophysiological conditions. Expression of AM, RAMP2, RAMP3 and CRLR mRNA was studied in the remnant kidney of rats with renal mass ablation using competitive quantitative RT-PCR techniques. Partial cloning was performed to determine the rat RAMP3 nucleotide sequence. In normal rat kidneys, expression levels of RAMP2, RAMP3, CRLR and AM mRNAs were 26.5 +/- 1.9 mmol/mole of GAPDH, 7.7 +/- 0.9 mmol/mole of GAPDH, 3.6 +/- 0.2 mmol/mole of GAPDH and 0.57 +/- 0.03 mmol/mole of GAPDH (mean +/- SE, n = 6), respectively. RAMP3 mRNA levels decreased significantly to about 50% and about 70% of control (sham-operated rats) 4 days and 14 days after 5/6 nephrectomy, respectively. CRLR mRNA levels also decreased significantly to about 30% and about 43% of control. Sodium intake restriction had no significant effects on the RAMP3 and CRLR gene expression. On the other hand, RAMP2 mRNA expression in the kidney was suppressed by sodium intake restriction regardless of nephrectomy, while RAMP2 levels in the remnant kidney were not significantly changed by 5/6 nephrectomy. Neither 5/6 nephrectomy or sodium intake restriction had any significant effects on the AM gene expression in the kidney. The present study showed that expression of mRNAs encoding AM, RAMP2, RAMP3 and CRLR were differentially regulated in remnant kidneys of rats with renal mass ablation.

摘要

肾上腺髓质素(AM)与利钠肽类似,具有血管舒张和利尿作用。AM受体复合物由降钙素受体样受体(CRLR)和受体活性修饰蛋白-2(RAMP2)或CRLR和RAMP3组成。我们旨在了解在病理生理条件下,肾脏中AM及AM受体复合物的基因表达是否受到调控。采用竞争性定量逆转录聚合酶链反应(RT-PCR)技术,研究了肾大部切除大鼠残余肾中AM、RAMP2、RAMP3和CRLR mRNA的表达。进行部分克隆以确定大鼠RAMP3的核苷酸序列。在正常大鼠肾脏中,RAMP2、RAMP3、CRLR和AM mRNA的表达水平分别为26.5±1.9 mmol/摩尔甘油醛-3-磷酸脱氢酶(GAPDH)、7.7±0.9 mmol/摩尔GAPDH、3.6±0.2 mmol/摩尔GAPDH和0.57±0.03 mmol/摩尔GAPDH(平均值±标准误,n = 6)。肾大部切除术后4天和14天,RAMP3 mRNA水平分别显著下降至对照组(假手术大鼠)的约50%和约70%。CRLR mRNA水平也显著下降至对照组的约30%和约43%。限制钠摄入对RAMP3和CRLR基因表达无显著影响。另一方面,无论是否进行肾大部切除术,限制钠摄入均会抑制肾脏中RAMP2 mRNA的表达,而肾大部切除术对残余肾中RAMP2水平无显著影响。肾大部切除术和限制钠摄入对肾脏中AM基因表达均无显著影响。本研究表明,在肾大部切除大鼠的残余肾中,编码AM、RAMP2、RAMP3和CRLR的mRNA表达受到不同调控。

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