Regulation of atrial natriuretic peptide receptors in vascular smooth muscle cells: Role of cGMP

L. M. Zhang, H. Tao, W. H. Newman

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

We tested the hypothesis that intracellular guanosine 3',5'-cyclic monophosphate (cGMP) regulates atrial natriuretic peptide (ANP) receptors. The effect of chronic exposure to ANP, sodium nitroprusside (SNP), and 8- bromo-cGMP (8-BrcGMP) on ANP receptors and cGMP formation was determined in guinea pig thoracic aorta smooth muscle cells (TASM) and in coronary artery smooth muscle cells (CASM). TASM express both the ANP-activated guanylyl cyclase (B-receptor) and the clearance receptor (C-receptor) and respond to ANP with increased cGMP. CASM exhibit only the ANP C-receptor. In TASM, 24-h treatment with 1 μM atriopeptin (AP) III [rat ANP-(103-126)] caused a sixfold increase in basal cGMP levels, which were unaltered in CASM. In AP III-treated TASM, maximal binding of 125I-labeled AP III (B(max)) was reduced 40% while affinity [dissociation constant (K(D))] was unaltered. In CASM, B(max) and K(D) were not affected. In treated TASM, washed free of AP III, acute dose-response curves of cGMP to AP III were not different from that in untreated cells. In both TASM and CASM, basal cGMP levels were elevated and B(max) was decreased by 6-h treatment with SNP. SNP did not alter the acute response of cGMP to AP III. In both cell types, 8-BrcGMP for 6 h caused reduction in B(max). These findings support the conclusion that elevated cGMP was necessary for ANP-induced downregulation of receptors. The unaltered responsiveness of cGMP to AP III suggests the B-receptor was not altered and the reduced B(max) was due to decreased C-receptor.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number6 33-6
StatePublished - Jan 1 1993

Keywords

  • 8- bromoguanosine 3',5'-cyclic monophosphate
  • atrial natriuretic peptide receptor regulation
  • particulate and soluble guanylyl cyclase
  • sodium nitroprusside
  • vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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