SPECIFIC RECEPTORS FOR ADRENOMEDULLIN IN CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS
SPECIFIC RECEPTORS FOR ADRENOMEDULLIN IN CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS
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DOI：
10.1016/0014-5793(94)80143-6
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发表时间：
1994-03-07
期刊：
影响因子：
3.5
通讯作者：
MARUMO, F
中科院分区：
文献类型：
--
作者：
EGUCHI, S;HIRATA, Y;MARUMO, F
本文研究了合成的大鼠肾上腺髓质素(Ram)对培养的大鼠血管平滑肌细胞(VSMC)受体结合和cAMP生成的影响。使用[I-125]Ram的结合研究表明，在VSMC中Ram存在单一的高亲和力(K-d 1.3×10(-8)M)结合位点。大鼠降钙素基因相关肽(RCGRP)的表观K-I为3×10~(-7)M。用[I-125]Ram亲和标记VSMC膜显示两条明显的标记带，表观分子量分别为120 kDa和70 kDa，这两条带均可被过量的未标记Ram或rCGRP消除。羊膜促cAMP生成的EC(50)约为10(-8)M，其作用与异丙肾上腺素相加，但不与rCGRP相加。心得安、吲哚美辛或奎尼克林不影响Ram诱导的cAMP反应，但可被CGRP受体拮抗剂人CGRP[8-37]抑制。这些结果表明，VSMC具有与腺苷环化酶功能偶联的AM受体，CGRP可与之相互作用。
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 [I-125]rAM revealed the presence of a single class of high-affinity (K-d 1.3 x 10(-8) M) binding sites for rAM in VSMC. The apparent K-i of rat calcitonin gene-related peptide (rCGRP) was 3 x 10(-7) M. Affinity labeling of VSMC membranes with [I-125]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 EC(50) 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 quinacrine, 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.