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Am J Physiol Gastrointest Liver Physiol 277: G314-G320, 1999;
0193-1857/99 $5.00
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Vol. 277, Issue 2, G314-G320, August 1999

Substance P inhibits pancreatic exocrine secretion via a neural mechanism

Kimberly S. Kirkwood, Edward H. Kim, Xiao Dong He, Edna Q. Calaustro, Christopher Domush, Shandra K. Yoshimi, Eileen F. Grady, John Maa, Nigel W. Bunnett, and Haile T. Debas

Departments of Surgery and Physiology, University of California School of Medicine, San Francisco, California 94143

We investigated the effects of the sensory neuropeptide substance P (SP) on amylase and fluid secretion in the isolated vascularly perfused rat pancreas. SP inhibited CCK-induced amylase release and secretin-induced juice flow via the pancreatic duct in a dose-related fashion. Threshold inhibition occurred following addition of 10-10 M SP to the perfusate, and maximal inhibition was seen with 10-8 M SP. The effects of SP were partially blocked by both the neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonists. Atropine and TTX blocked SP-induced effects on both amylase secretion (26 and 63% blockade, respectively) and pancreatic juice flow (21 and 79% blockade, respectively). Excitation of pancreatic sensory nerves using capsaicin (in the absence of SP) inhibited both amylase and pancreatic juice flow via activation of the NK1 receptor. We conclude that SP inhibits exocrine secretion via an indirect neural mechanism.

sensory nerves; pancreatic juice; tachykinins; neurokinin receptors; amylase


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