A key role of neurokinin 1 receptors in acute pancreatitis and associated lung injury.

Abstract

Earlier studies have shown that mice deficient in NK1 receptors or its ligand, substance P, are protected against acute pancreatitis and associated lung injury. In the current study, the protective effect of NK1 receptor blockage against acute pancreatitis and associated lung injury was investigated, using a specific receptor antagonist, CP-96345. Acute pancreatitis was induced in mice by intraperitoneal (i.p.) injections of caerulein. Substance P levels in plasma, pancreas, and lungs were found to be elevated in a caerulein dose-dependent manner. Mice treated with CP-96345, either prophylactically, or therapeutically, were protected against acute pancreatitis and associated lung injury as evident by attenuation in plasma amylase, pancreatic and pulmonary myeloperoxidase activities, and histological evidence of pancreatic and pulmonary injuries. Pulmonary microvascular permeability was also reduced as a result of CP-96345 treatment. These results point to a key role of NK1 receptors in acute pancreatitis and associated lung injury.

• Authors: Hon Yen Lau, Fei Ling Wong, Madhav Bhatia
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 327 Issue 2 Pg. 509-15 (Feb 11 2005) ISSN: 0006-291X [Print] United States
• PMID: 15629143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biphenyl Compounds
• Neurokinin-1 Receptor Antagonists
• Receptors, Neurokinin-1
• Substance P
• Ceruletide
• Peroxidase
• Amylases
• CP 96345

Topics

• Amylases (blood)
• Animals
• Biphenyl Compounds (administration & dosage, pharmacology, therapeutic use)
• Capillary Permeability (drug effects)
• Ceruletide (pharmacology)
• Lung (drug effects, metabolism, pathology)
• Lung Diseases (complications, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Neurokinin-1 Receptor Antagonists
• Pancreatitis (complications, drug therapy, metabolism, pathology)
• Peroxidase (metabolism)
• Receptors, Neurokinin-1 (metabolism)
• Substance P (metabolism)
• Time Factors