Elsevier

FEBS Letters

Volume 248, Issues 1–2, 8 May 1989, Pages 28-34
FEBS Letters

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

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Abstract

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 Ki 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 pA2 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.

Keywords

Atrial natriuretic peptide analog
Atrial natriuretic peptide receptor antagonist
Receptor binding
cyclic GMP production
Vasorelaxation
(Cultured vascular smooth muscle cell)

Abbreviations

Acm, acetamidomethyl
ANP, atrial natriuretic peptide
Boc, tert-butyloxycarbonyl
Bzl, benzyl
cGMP, guanosine 3′,5′-cyclic monophosphate
Dcb, 2,6-dichlorobenzyl
DCC, dicyclohexylcarbodiimide
EDC, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
HOBt, 1-hydroxybenzotriazole
HOSu, N-hydroxysuccinimide
HPLC, high-performance liquid chromatography
PGF, prostaglandin F
TFA, trifluoroacetic acid
VSMC, cultured vascular smooth muscle cells

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