Biochemical and Biophysical Research Communications
A key role of neurokinin 1 receptors in acute pancreatitis and associated lung injury
Section snippets
Materials and methods
Induction of acute pancreatitis. All experimental procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animal (NIH Publication, 1996). Caerulein was obtained from Bachem (Bubendorf, Switzerland). Balb/C mice (20–25 g) were randomly assigned to control or experimental groups using 10 or more animals for each group. Animals were given hourly intraperitoneal (i.p.) injections of normal saline or saline containing caerulein (50 μg kg−1 h−1) for 10 h. CP-96345
Effect of induction of acute pancreatitis on pancreas, lung, and plasma levels of substance P
Hyperstimulation of the pancreas by intraperitoneal administration of caerulein at a dose of 50 μg kg−1 hourly for 3, 6, and 10 h to mice resulted in acute necrotizing pancreatitis as characterized by severe edema, vacuolization, neutrophil infiltration, and acinar necrosis in the pancreas. Moreover, alveolar wall thickening, neutrophil infiltration, and increased cellularity indicated the lung injury associated with this condition. Substance P levels in pancreas, lung, and plasma samples of mice
Discussion
Substance P is a major mediator of neurogenic inflammation, in several tissues, including skin, cardiovascular tissue, cephalic structures, respiratory tract, genitourinary tract, and gastrointestinal tract [6]. NKA has also been shown to play an important role in neurogenic inflammation in several conditions [6]. Indeed, neurogenic inflammation likely underlies several disease conditions, such as asthma, immune-complex-mediated lung injury, experimental arthritis, and inflammatory bowel
Acknowledgments
The authors thank Mei Leng Shoon and Jiali Huang for help with the animal experiments and substance P extraction. The manuscript is supported by Academic Research Fund Grant No. R-184-000-054-112 and Biomedical Research Council Grant No. R-184-000-069-305.
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2012, Respiratory MedicineCitation Excerpt :Similar findings have been observed in mice treated with the specific NK-1R antagonist, CP-96345. Pulmonary microvascular permeability was also reduced as a result of CP-96345 treatment.102 Deletion of the substance P gene precursor preprotachykinin-A (PPT-A) has a protective effect against acute pancreatitis-associated lung injury, with a partial protection against local pancreatic damage.103
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These two authors contributed equally to the work.