Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart.
Expression of urocortin and corticotropin-releasing factor receptor subtypes in the human heart.
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DOI：
10.1210/jcem.87.1.8160
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Y. Kimura;Kazuhiro Takahashi;K. Totsune;Y. Muramatsu;C. Kaneko;A. Darnel;Takashi Suzuki;M. Ebina;T. Nukiwa;H. Sasano
中科院分区：
文献类型：
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作者：
Y. Kimura;Kazuhiro Takahashi;K. Totsune;Y. Muramatsu;C. Kaneko;A. Darnel;Takashi Suzuki;M. Ebina;T. Nukiwa;H. Sasano
尿皮质素（Urocortin，Ucn）是促肾上腺皮质激素释放因子（corticotropin-releasing factor，CRF）神经肽家族的新成员，在大鼠心脏具有正性肌力作用和抗缺血作用。Ucn以非常高的亲和力结合CRF受体1型（CRF-R1）和CRF受体2型（CRF-R2）。然而，迄今为止，在人类心脏中表达的CRF受体的内源性配体尚未阐明。因此，在这项研究中，我们研究了UCN和CRF受体的表达在人心脏尸检获得的RT-PCR，免疫组化和RIA。RT-PCR分析表明，Ucn和CRF-R2 α mRNA在所有四个室中均被检测到。CRF-R1 mRNA在一些左心房、左心室和一个右心室中微弱存在。CRF-R2 β mRNA主要在左心房表达。在四个腔室中均未检测到CRF mRNA。在所有四个腔室的心肌细胞中检测到Ucn和CRF受体的免疫染色。通过RIA在所有四个腔室中检测到Ucn样免疫反应性，其中左心室中的浓度最高（1.90 +/- 0.5 pmol/g湿重，平均值+/- SEM; n = 4）。另一方面，CRF样免疫反应性在人类心脏中非常低或检测不到。SephadexG-50柱层析表明，大多数人心脏中的Ucn样免疫反应性洗脱早于标准Ucn，在Ucn的位置有一个小峰。免疫组化和放射免疫分析均未检测到骨骼肌UCN免疫反应。这些结果表明，UCN在人体心脏中产生，并主要以较大分子量的形式储存在那里。因此，内源性产生的Ucn可能主要通过CRF-R2以自分泌和/或旁分泌的方式在人心脏中发挥其作用。
Urocortin (Ucn) is a new member of the corticotropin-releasing factor (CRF) neuropeptide family and has positive inotropic actions and protective effects against ischemia in the rat heart. Ucn binds with very high affinity to both CRF receptor type 1 (CRF-R1) and CRF receptor type 2 (CRF-R2). However, to date, endogenous ligand(s) for CRF receptors expressed in the human heart have yet to be elucidated. In this study, we therefore examined the expression of Ucn and CRF receptors in human heart obtained at autopsy by RT-PCR, immunohistochemistry, and RIA. RT-PCR analysis demonstrated that Ucn and CRF-R2alpha mRNAs were detected in all four chambers. CRF-R1 mRNA was weakly present in some left atria, left ventricles, and in one right ventricle. CRF-R2beta mRNA was detected predominantly in the left atrium. CRF mRNA was not detected in any of the four chambers. Immunostaining for both Ucn and CRF receptors was detected in cardiac myocytes in all four chambers. Ucn-like immunoreactivity was detected in all four chambers by RIA, with the highest concentrations in the left ventricle (1.90 +/- 0.5 pmol/g wet weight, mean +/- SEM; n = 4). On the other hand, CRF-like immunoreactivity was very low or undetectable in the human heart. Sephadex G-50 column chromatography demonstrated that most of the Ucn-like immunoreactivity in the human heart was eluting earlier than the standard Ucn, with one minor peak in the position for Ucn. Ucn immunoreactivity was not detected in skeletal muscle by immunohistochemistry or RIA. These results suggest that Ucn is produced in the human heart and stored there mainly in the larger molecular weight forms. Endogenously produced Ucn may therefore exert its effects mostly through CRF-R2 in an autocrine and/or paracrine manner in the human heart.