Abstract:
: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 (Kd 1.3 x 10(-8) M) binding sites for rAM in VSMC. The apparent Ki of rat calcitonin gene-related peptide (rCGRP) was 3 x 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 propranolol, 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.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Eguchi S,Hirata Y,Kano H,Sato K,Watanabe Y,Watanabe TX,Nakajima K,Sakakibara S,Marumo Fdoi
10.1016/0014-5793(94)80143-6subject
Has Abstractpub_date
1994-03-07 00:00:00pages
226-30issue
3eissn
0014-5793issn
1873-3468pii
0014-5793(94)80143-6journal_volume
340pub_type
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