Nishikimi T, Miyata A, Horio T, Yoshihara F, Nagaya N, Takishita S, Yutani C, Matsuo H, Matsuoka H, Kangawa K
Research Institute, National Cardiovascular Center, Suita, Osaka 565, Japan.
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H3031-9. doi: 10.1152/ajpheart.2000.279.6.H3031.
In the present study we investigated the form of expression, action, second messenger, and the cellular location of urocortin, a member of the corticotropin-releasing factor (CRF) family, in the heart. Urocortin mRNA, as shown by quantitative RT-PCR analysis, is expressed in the cultured rat cardiac nonmyocytes (NMC) as well as myocytes (MC) in the heart, whereas CRF receptor type 2beta (CRF-R2beta), presumed urocortin receptor mRNA, is predominantly expressed in MC compared with NMC. Urocortin mRNA expression is higher in left ventricular (LV) hypertrophy than in normal LV, whereas CRF-R2beta mRNA expression is markedly depressed in LV hypertrophy compared with normal LV. Urocortin more potently increased the cAMP levels in both MC and NMC than did CRF, and its effect was more potent in MC than in NMC. Urocortin significantly increased protein synthesis by [(14)C]Phe incorporations and atrial natriuretic peptide secretion in MC and collagen and increased DNA synthesis by [(3)H]prolin and [(3)H]Thy incorporations in NMC. An immunohistochemical study revealed that urocortin immunoreactivity was observed in MC in the normal human heart and that it was more intense in the MC of the human failing heart than in MC of the normal heart. These results, together with the recent evidence of urocortin for positive inotropic action, suggest that increased urocortin in the diseased heart may modulate the pathophysiology of cardiac hypertrophy or failing heart, at least in part, via cAMP signaling pathway.
在本研究中，我们调查了促肾上腺皮质激素释放因子（CRF）家族成员尿皮质素在心脏中的表达形式、作用、第二信使以及细胞定位。定量逆转录聚合酶链反应（RT-PCR）分析显示，尿皮质素mRNA在培养的大鼠心脏非心肌细胞（NMC）以及心肌细胞（MC）中均有表达，而推测为尿皮质素受体mRNA的2β型CRF受体（CRF-R2β）在MC中的表达明显高于NMC。与正常左心室相比，左心室肥厚时尿皮质素mRNA表达升高，而CRF-R2β mRNA表达明显降低。与CRF相比，尿皮质素更有效地增加了MC和NMC中的环磷酸腺苷（cAMP）水平，且其在MC中的作用比在NMC中更显著。尿皮质素通过[（14）C]苯丙氨酸掺入显著增加了MC中的蛋白质合成和心房利钠肽分泌，通过[（3）H]脯氨酸和[（3）H]胸腺嘧啶掺入增加了NMC中的DNA合成。免疫组织化学研究显示，在正常人心肌细胞中可观察到尿皮质素免疫反应性，且在心力衰竭患者的心肌细胞中比正常心肌细胞中的反应更强。这些结果，连同近期关于尿皮质素具有正性肌力作用的证据，提示患病心脏中尿皮质素增加可能至少部分地通过cAMP信号通路调节心脏肥大或心力衰竭的病理生理过程。
