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

Biochem Biophys Res Commun. 2005 Feb 11;327(2):509-15. doi: 10.1016/j.bbrc.2004.12.030.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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