Makino I, Honda K, Makino Y, Okano I, Kangawa K, Kamiya H, Shibata K, Kawarabayashi T
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan.
Biochem Biophys Res Commun. 2001 Nov 2;288(3):515-20. doi: 10.1006/bbrc.2001.5805.
Adrenomedullin is known to inhibit cell proliferation in cultured rat vascular smooth muscle cells, through a cAMP-dependent process. The calcitonin receptor-like receptor could function as an adrenomedullin receptor when co-expressed with receptor activity-modifying protein 2. To determine whether vascular adrenomedullin receptor components, the calcitonin receptor-like receptor and the receptor activity-modifying protein 2, phenotypically change during in vitro culture conditions, we examined the expression of adrenomedullin receptor components, adrenomedullin-induced cAMP production, and the inhibition of cell proliferation in culture rat vascular smooth muscle cells during serial passages. The results demonstrated that the receptor activity-modifying protein 2 and calcitonin receptor-like receptor mRNAs increased in a passage-dependent manner in rat vascular smooth muscle cells. Furthermore, the responses of both the elevation of cAMP and the inhibition of cell proliferation became larger in vascular smooth muscle cells with an increasing number of passages. The results suggest that the increase in functional AM receptor during phenotypic change may in part contribute to the development of vascular lesions, such as in atherosclerosis.
已知肾上腺髓质素可通过依赖环磷酸腺苷（cAMP）的过程抑制培养的大鼠血管平滑肌细胞增殖。降钙素受体样受体与受体活性修饰蛋白2共表达时可作为肾上腺髓质素受体发挥作用。为了确定血管肾上腺髓质素受体成分，即降钙素受体样受体和受体活性修饰蛋白2，在体外培养条件下是否发生表型变化，我们检测了连续传代培养的大鼠血管平滑肌细胞中肾上腺髓质素受体成分的表达、肾上腺髓质素诱导的cAMP生成以及细胞增殖抑制情况。结果表明，受体活性修饰蛋白2和降钙素受体样受体mRNA在大鼠血管平滑肌细胞中呈传代依赖性增加。此外，随着传代次数增加，血管平滑肌细胞中cAMP升高和细胞增殖抑制的反应均变得更大。结果提示，表型变化过程中功能性肾上腺髓质素受体的增加可能部分促成了血管病变的发展，如动脉粥样硬化。
