A dicarba analog of beta-atrial natriuretic peptide (beta-ANP) inhibits guanosine 3',5'-cyclic monophosphate production induced by alpha-ANP in cultured rat vascular smooth muscle cells

FEBS Lett. 1989 May 8;248(1-2):28-34. doi: 10.1016/0014-5793(89)80425-9.

Abstract

The synthesis and biological properties are described of [Asu7,23']-beta-ANP-(7-28) (Asu, L-alpha-aminosuberic acid), a dicarba analog of beta-atrial natriuretic peptide (beta-ANP, an antiparallel dimer of human alpha-ANP with the chains linked by 7-23' and 7'-23 disulfide bonds). This Asu-analog (referred to as analog III) displaced 125I-alpha-ANP specifically bound to cultured rat vascular smooth muscle cells (VSMC) with an apparent Ki of 2.1 x 10(-8) M, but did not stimulate formation of intracellular cGMP at 10(-8) -10(-5) M. Analog III inhibited the alpha-ANP-stimulated cGMP production in VSMC competitively with a pA2 value of 7.45 and behaved as an antagonist of alpha-ANP in rat aorta smooth muscle relaxation. In addition, beta-ANP was also shown to inhibit the alpha-ANP-induced cGMP production in a dose-dependent manner. The mechanism of action of beta-ANP is also discussed.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Atrial Natriuretic Factor / analogs & derivatives
  • Atrial Natriuretic Factor / pharmacology*
  • Binding, Competitive
  • Cells, Cultured
  • Cyclic GMP / biosynthesis*
  • Dose-Response Relationship, Drug
  • Humans
  • Male
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Rats
  • Rats, Inbred Strains

Substances

  • Atrial Natriuretic Factor
  • Cyclic GMP