Inhibition of cyclooxygenase-2 by natriuretic peptides

Alexandra K. Kiemer, Martin D. Lehner, Thomas Hartung, Angelika M. Vollmar

Research output: Contribution to journalArticle

Abstract

The atrial natriuretic peptide (ANP) has been suggested to possess immunomodulatory potential because of its property to alter macrophage functions via its guanylate-cylcase-coupled A-receptor (NPR-A), such as inhibiting the expression of inducible nitric oxide synthase or TNF-α. The aim of this study was to investigate whether ANP influences COX-2. COX-2 expression in murine macrophages and in mice was induced by lipopolysaccharide. Release of PGE2 and thromboxane B2 was significantly reduced in the presence of ANP. C-type natriuretic peptide (CNP) also significantly reduced PGE2-accumulation in macrophages. Northern and Western blots showed that ANP attenuates COX-2 mRNA and protein. Reduction of neither COX-2 nor of PGE2 production was significantly abrogated by an NPR-A antagonist, suggesting a pathway independent of cGMP. Furthermore, dibutyryl-cGMP did not affect PGE2-accumulation. cANF, the specific ligand for the natriuretic peptide (NP) clearance-receptor (NPR-C), significantly inhibited PGE2-production. Because some biological activities of ANP have been reported to be mediated via an NPR-C-mediated inhibition of adenylate-cyclase, we determined cAMP levels. ANP, CNP, and cANF significantly attenuated intracellular cAMP. In summary, ANP was shown to attenuate PGE2-production of lipopolysaccharide-activated macrophages predominantly via the NP clearance-receptor. ANP reduces COX-2-protein and -mRNA levels. The inhibition seems to be mediated via NPR-C and related to an attenuation of cAMP production.

Original languageEnglish (US)
Pages (from-to)846-852
Number of pages7
JournalEndocrinology
Volume143
Issue number3
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Endocrinology

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