A dicarba analog of β‐atrial natriuretic peptide (β‐ANP) inhibits guanosine 3′,5′‐cyclic monophosphate production induced by α‐ANP in cultured rat vascular smooth muscle cells

摘要

>The synthesis and biological properties are described of [Asu7,23′]-β-ANP-(7–28) (Asu, L-α-aminosuberic acid), a dicarba analog of β-atrial natriuretic peptide (β-ANP, an antiparallel dimer of human α-ANP with the chains linked by 7–23′ and 7′–23 disulfide bonds). This Asu-analog (referred to as analog III) displaced 125I-α-ANP specifically bound to cultured rat vascular smooth muscle cells (VSMC) with an apparent K _i of 2.1 × 10−8 M, but did not stimulate formation of intracellular cGMP at 10−8–10−5 M. Analog III inhibited the α-ANP-stimulated cGMP production in VSMC competitively with a pA ₂ value of 7.45 and behaved as an antagonist of α-ANP in rat aorta smooth muscle relaxation. In addition, β-ANP was also shown to inhibit the α-ANP-induced cGMP production in a dose-dependent manner. The mechanism of action of β-ANP is also discussed.