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Am J Physiol Gastrointest Liver Physiol 294: G1452, 2008; doi:10.1152/ajpgi.90251.2008
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LETTERS TO THE EDITOR

Reply to Lechin and van der Dijs

Rajinder Dawra and Ashok Saluja

Department of Surgery, University of Minnesota, Minneapolis, Minnesota

Submitted 24 March 2008 ; accepted in final form 31 March 2008

WE APPRECIATE THE INTEREST in and thought-provoking discussion about the possible mechanism of L-arginine-induced pancreatitis as it relates to our recently published paper (1). In this study, we hypothesize that excessive peroxynitrite formation as result of high doses of L-arginine could cause acinar cell injury and pancreatitis. This was based on our observations that administering either D-arginine or other amino acids at comparable doses did not induce pancreatitis. Furthermore, L-arginine at lower doses did not induce pancreatitis.

Lechin and van der Dijs (2) suggest that L-arginine might induce pancreatitis by the autonomous nervous system. This is based on their observation that a small oral dose of L-arginine (50 mg) is able to provoke significant changes in plasma neurotransmitters. This could cause hypersecretion, which cannot be drained through the pancreatic duct because of the norepinephrine contractile effect by sympathetic nerves. We have not measured plasma neurotransmitters in our experiments, but had this been the mechanism we should have observed some changes in pancreatitis markers with lower doses of L-arginine. Moreover, in our preliminary studies on acinar cells prepared 24 h after L-arginine administration, the secretory response to the cholecystokinin analog caerulein decreased, which again indicates a secretory block at the acinar cell level rather than at the ductal level. In a rat model of L-arginine-induced pancreatitis, antioxidants decrease pancreatic injury. Thus peroxynitrite appears to be a strong contender for mechanism of L-arginine-induced pancreatitis.

FOOTNOTES


Address for reprint requests and other correspondence: A. K. Saluja, Dept. of Surgery, Univ. of Minnesota, MMC 195, 420 Delaware St. SE, Minneapolis, MN 55455 (e-mail: asaluja{at}umn.edu)

REFERENCES

  1. Dawra R, Sharif R, Phillips P, Dudeja V, Dhaulakhandi D, Saluja AK. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am J Physiol Gastrointest Liver Physiol 292: G1009–G1018, 2007.[Abstract/Free Full Text]
  2. Lechin F, van der Dijs B. Arginine-induced pancreatitis: involvement of the autonomic nervous system? Am J Physiol Gastrointest Liver Physiol. doi: 10.1152/ajpgi.00327.2007.[Free Full Text]




This Article
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