A newly identified human peptide, adrenomedullin (AM) increased cAMP levels with dose and time dependencies in a manner similar to that of human calcitonin gene-related peptide (CGRP) in rat vascular smooth muscle cells (VSMC). The EC(50) value of human AM is 2 X 10(-8)M which is slightly higher than that of CGRP (8.5 X 10(-9)M). In a receptor binding assay for AM in rat VSMC, the binding of [I-125] AM was competitively inhibited by human AM, but not by human CGRP. Thus, AM is thought to increase intracellular cAMP in rat VSMC via its specific receptor to evoke vasodilation. (C) 1994 Academic Press, Inc.