James W Suliburk1, David W Mercer. 1. Department of General Surgery, The University of Texas Medical School at Houston, Houston, Texas, USA. James.W.Suliburk@uth.tmc.edu
Abstract
BACKGROUND: Ketamine exerts anti-inflammatory actions and attenuates lipopolysaccharide (LPS)-induced gastric dysfunction by an unknown mechanism. Because stress-inducible phosphoproteins mediate many inflammatory responses, we hypothesized that ketamine would disrupt the early signaling events of LPS-induced inflammation by altering phosphorylation of stress-inducible phosphoproteins JNK, p38, and IkB. METHODS: Adult rats received saline or ketamine (70 mg/kg, intraperitoneal) 1 hour before LPS (20 mg/kg, intraperitoneal) or saline. Animals were killed at 15, 30, 45, and 60 minutes after LPS, gastric mucosa was harvested, and gastric volume and pH were recorded. Gastric mucosal phosphorylation of JNK, p38, and IkB-alpha were analyzed with a multiplexed suspension immunoassay. RESULTS: Ketamine-attenuated LPS induced increases in gastric luminal fluid and pH. Control animals receiving saline or ketamine and no LPS had gastric volumes of 0.1 mL and luminal pH of 2 at all time points. LPS upregulated phosphorylation of JNK, p38, and IkB-alpha as early as 15 minutes after LPS. Ketamine did not effect the early phosphorylation of these proteins. CONCLUSION: Endotoxin causes gastric dysfunction and upregulates stress-inducible phosphoproteins within minutes after LPS. Although ketamine attenuates gastric dysfunction, its salutary effects do not seem to be related to alterations in phosphorylation of JNK, p38, or IkB-alpha.
BACKGROUND:Ketamine exerts anti-inflammatory actions and attenuates lipopolysaccharide (LPS)-induced gastric dysfunction by an unknown mechanism. Because stress-inducible phosphoproteins mediate many inflammatory responses, we hypothesized that ketamine would disrupt the early signaling events of LPS-induced inflammation by altering phosphorylation of stress-inducible phosphoproteins JNK, p38, and IkB. METHODS: Adult rats received saline or ketamine (70 mg/kg, intraperitoneal) 1 hour before LPS (20 mg/kg, intraperitoneal) or saline. Animals were killed at 15, 30, 45, and 60 minutes after LPS, gastric mucosa was harvested, and gastric volume and pH were recorded. Gastric mucosal phosphorylation of JNK, p38, and IkB-alpha were analyzed with a multiplexed suspension immunoassay. RESULTS:Ketamine-attenuated LPS induced increases in gastric luminal fluid and pH. Control animals receiving saline or ketamine and no LPS had gastric volumes of 0.1 mL and luminal pH of 2 at all time points. LPS upregulated phosphorylation of JNK, p38, and IkB-alpha as early as 15 minutes after LPS. Ketamine did not effect the early phosphorylation of these proteins. CONCLUSION: Endotoxin causes gastric dysfunction and upregulates stress-inducible phosphoproteins within minutes after LPS. Although ketamine attenuates gastric dysfunction, its salutary effects do not seem to be related to alterations in phosphorylation of JNK, p38, or IkB-alpha.