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Acute hypothalamo-pituitary-adrenal axis response to LPS-induced endotoxemia: expression pattern of kinin type B1 and B2 receptors

Författare

  • Fatimunnisa Qadri
  • Florian Rimmele
  • Lisa Mallis
  • Walter Haeuser
  • Andreas Dendorfer
  • Olaf Joehren
  • Peter Dominiak
  • Fredrik Leeb-Lundberg
  • Michael Bader

Summary, in English

Bradykinin (BK) and des-Arg(9)-BK are pro-inflammatory mediators acting via B2 (B2R) and B1 (B1R) receptors, respectively. We investigated the role of B2R and B1R in lipopolysaccharide (LPS)-induced hypothalamopituitary-adrenal (HPA) axis activation in SD rats. LPS given intraperitoneally (ip) up-regulated B1R mRNA in the hypothalamus, both B1R and B2R were up-regulated in pituitary and adrenal glands. Receptor localization was performed using immunofluorescence staining. B1R was localized in the endothelial cells, nucleus supraopticus (SON), adenohypophysis and adrenal cortex. B2R was localized nucleus paraventricularis (PVN) and SON, pituitary and adrenal medulla. Blockade of B1R prior to LPS further increased ACTH release and blockade of B1R 1 h after LPS decreased its release. In addition, we evaluated if blockade of central kinin receptors influence the LPS-induced stimulation of hypothalamic neurons. Blockade of both B1R and B2R reduced the LPS-induced c-Fos immunoreactivity in the hypothalamus. Our data demonstrate that a single injection of LPS induced a differential expression pattern of kinin B1R and B2R in the HPA axis. The tissue specific cellular localization of these receptors indicates that they may play a crucial role in the maintenance of body homeostasis during endotoxemia.

Avdelning/ar

  • Drug Target Discovery
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publiceringsår

2016

Språk

Engelska

Sidor

97-109

Publikation/Tidskrift/Serie

Biological Chemistry

Volym

397

Issue

2

Dokumenttyp

Artikel i tidskrift

Förlag

De Gruyter

Ämne

  • Pharmacology and Toxicology

Nyckelord

  • B1R
  • B2R
  • c-Fos
  • HPA-axis
  • receptor localization
  • sepsis

Status

Published

Forskningsgrupp

  • Drug Target Discovery

ISBN/ISSN/Övrigt

  • ISSN: 1437-4315