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

Author

  • 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.

Department/s

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

Publishing year

2016

Language

English

Pages

97-109

Publication/Series

Biological Chemistry

Volume

397

Issue

2

Document type

Journal article

Publisher

De Gruyter

Topic

  • Pharmacology and Toxicology

Keywords

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

Status

Published

Research group

  • Drug Target Discovery

ISBN/ISSN/Other

  • ISSN: 1437-4315