Kato J, Kitamura K, Kangawa K, Eto T
First Department of Internal Medicine, Miyazaki Medical College, Japan.
Eur J Pharmacol. 1995 Apr 28;289(2):383-5. doi: 10.1016/0922-4106(95)90117-5.
Accumulation of the intracellular cyclic AMP (cAMP) was measured in cultured endothelial cells of the human umbilical vein following the incubation with adrenomedullin, a newly discovered hypotensive peptide, to determine the presence of specific receptors for adrenomedullin. Adrenomedullin increased the intracellular cAMP in a dose-dependent fashion in the endothelial cells, and the EC50 value was as low as 10(-9) M. Calcitonin gene-related peptide (CGRP) that has a homology to adrenomedullin in its amino-acid sequence also increased the intracellular cAMP with an EC50 value greater than 10(-7) M. The effect of CGRP was attenuated in the presence of CGRP-(8-37), a CGRP receptor antagonist. However, CGRP-(8-37) had no effect on the cAMP accumulation by adrenomedullin. These findings indicate that the cultured endothelial cells of human umbilical vein possess specific adrenomedullin receptors coupled with the adenylate cyclase activity that may have little affinity with CGRP.
为了确定肾上腺髓质素（一种新发现的降压肽）特异性受体的存在，我们检测了培养的人脐静脉内皮细胞中细胞内环磷酸腺苷（cAMP）的积累情况。肾上腺髓质素在内皮细胞中以剂量依赖方式增加细胞内cAMP，其半数有效浓度（EC50）低至10^(-9) M。在氨基酸序列上与肾上腺髓质素有同源性的降钙素基因相关肽（CGRP）也能增加细胞内cAMP，但其EC50值大于10^(-7) M。CGRP受体拮抗剂CGRP-(8 - 37)存在时，CGRP的作用减弱。然而，CGRP-(8 - 37)对肾上腺髓质素引起的cAMP积累没有影响。这些发现表明，培养的人脐静脉内皮细胞具有与腺苷酸环化酶活性偶联的特异性肾上腺髓质素受体，该受体可能与CGRP亲和力较低。
