Modulation of endothelial prostaglandin synthesis by corticotropin releasing factor and antagonists

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Corticotropin releasing factor (CRF) is a hypothalamic hormone that also displays autocrine/paracrine roles at peripheral sites. High concentrations of CRF have been identified in endothelial cells and other inflammatory tissues. We investigated the effects of CRF and antagonists in the regulation of prostaglandin synthesis in bovine aortic endothelial cells, and also characterized the binding of CRF in these cells. Interleukin-1α increased prostacyclin (prostaglandin I2) synthesis in endothelial cells and this response to interleukin-1α was abolished by simultaneous exposure to CRF. The effect of CRF on interleukin-1α-induced prostaglandin synthesis was antagonised by the CRF receptor antagonist α-helical CRF-(9-41). In addition, this as well as another CRF receptor antagonist, namely [d-Phe12]CRF-(12-41), when applied alone at low concentrations inhibited the interleukin-1α-induced prostaglandin synthesis similarly to CRF, suggesting partial agonistic action. Binding of [125I]-labeled CRF in endothelial cells was saturable and fitted a two sites model. K(d) for the higher-affinity class of receptors was 0.2±0.02 nM, and B(max) 0.79±0.095 fmol/mg protein. The lower-affinity class of receptors had a K(d) of 1.77±0.14 μM and B(max) 0.97±0.12 fmol/mg protein. These findings suggest a direct role for CRF in the local regulation of inflammation. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)297-302
Number of pages6
JournalEuropean Journal of Pharmacology
Volume353
Issue number2-3
DOIs
StatePublished - 24 Jul 1998
Externally publishedYes

Keywords

  • CRF (corticotropin releasing factor)
  • CRF receptor
  • CRF-(9-41), α-helical
  • Endothelium
  • Interleukin-1
  • [d-Phe]CRF-(12-41)

Fingerprint

Dive into the research topics of 'Modulation of endothelial prostaglandin synthesis by corticotropin releasing factor and antagonists'. Together they form a unique fingerprint.

Cite this