Lack of effect of proteinase-activated receptor-2 (PAR-2) deletion on the pathophysiological changes produced by lipopolysaccharide in the mouse: comparison with dexamethasone.
This study tested the hypothesis that activation of proteinase-activated receptor-2 (PAR-2) contributes towards the pathophysiology of lipopolysaccharide (LPS)-induced shock in the mouse. The effects of LPS on plasma glucose, biochemical markers of hepatic, renal and pancreatic exocrine function and lung content of myeloperoxidase (MPO) were examined in homozygous PAR-2 knockout mice (PAR-2 -/-) and genetically equivalent, homozygous PAR-2 +/+ mice. The effect of LPS was also examined in normal mice receiving dexamethasone (10 mg kg(-1), i. p.) or saline as a positive control. At six hours after intraperitoneal injection, LPS (40 mg kg(-1)) produced an increase in rectal temperature, hypoglycaemia and elevations in serum concentrations of alanine aminotransferase (ALT), creatinine and lipase, as well as an increase in lung MPO content. Dexamethasone treatment reduced LPS-induced hypoglycaemia and elevation of serum ALT concentrations but did not modify elevations in serum creatinine and lipase concentrations or the increase in lung MPO content. The changes in serum concentrations of glucose, ALT, creatinine and lipase produced by LPS in PAR-2 -/- mice were not different from those seen in wild-type or PAR-2 +/+ mice. These data suggest that activation of PAR-2 may not play a pivotal role in LPS-induced multi-organ dysfunction.
Kazerani
Hamid Reza
HR
Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, John Arbuthnott Building, University of Strathclyde, Taylor Street, Glasgow G4 0NR, Scotland, UK.
Plevin
Robin
R
Kawagoe
Junichi
J
Kanke
Toru
T
Furman
Brian L
BL
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003907:Dexamethasone / Q000627:therapeutic use*; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D044464:Receptor, PAR-2 / Q000172:deficiency / Q000502:physiology*
D001786:Blood Glucose; D008070:Lipopolysaccharides; D044464:Receptor, PAR-2; D003907:Dexamethasone; D003404:Creatinine