Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells

FEBS Letters

Sakakibara, Shumpei²  Eguchi, Satoru³  Hirata, Yukio³  Kano, Hiroaki³  Marumo, Fumiaki³  Watanabe, Yukihiko¹  Watanabe, Takushi X.²  Nakajima, Kiichiro²  Sato, Kyoko¹ 

[1] SRL Inc., Komiya-chou 51, Hachioji-shi, Tokyo 192, Japan;Peptide Institute Inc., Protein Research Foundation, 4-1-2 Ina, Minoh-shi, Osaka 565, Japan;Second Department of Internal Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113, Japan

关键词: Adrenomedullin;    Calcitonin gene-related peptide;    Receptor;    Cyclic AMP;    Affinity labelling;    Rat vascular smooth muscle cell;   

DOI  :  10.1016/0014-5793(94)80143-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The effects of synthetic rat adrenomedullin (rAM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma, on receptor binding and cAMP generation were studied in cultured rat vascular smooth muscle cells (VSMC). A binding study using [¹²⁵I]rAM revealed the presence of a single class of high-affinity (K _d1.3 × 10⁻⁸ M) binding sites for rAM in VSMC. The apparent K _i of rat calcitonin gene-related peptide (rCGRP) was 3 × 10⁻⁷ M. Affinity labeling of VSMC membranes with [¹²⁵I]rAM revealed two distinct labeled bands with apparent molecular weights of 120 and 70 kDa, both of which were abolished by excess unlabeled rAM or rCGRP. rAM stimulated cAMP formation with an approximate EC₅₀ of 10⁻⁸ M, the effect of which was additive with isoproterenol, but not with rCGRP. The rAM-induced cAMP response was unaffected by propranalol, indomethacin, or quinaerine, but inhibited by a CGRP receptor antagonist, human CGRP[8–37]. These data suggest that VSMC possesses specific AM receptors functionally coupled to adenylate cyclase with which CGRP interacts.

【 授权许可】

Unknown