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

Biol Chem. 2016 Jan 1;397(2):97-109. doi: 10.1515/hsz-2015-0206.


Bradykinin (BK) and des-Arg9-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 hypothalamo-pituitary-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.

MeSH terms

  • Acute Disease
  • Animals
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endotoxemia / chemically induced
  • Endotoxemia / metabolism*
  • Homeostasis / drug effects
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism*
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology
  • Male
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Bradykinin B1 / analysis
  • Receptor, Bradykinin B1 / biosynthesis*
  • Receptor, Bradykinin B1 / metabolism
  • Receptor, Bradykinin B2 / analysis
  • Receptor, Bradykinin B2 / biosynthesis*
  • Receptor, Bradykinin B2 / metabolism


  • Lipopolysaccharides
  • Receptor, Bradykinin B1
  • Receptor, Bradykinin B2