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, Haile T. Debas

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)G314-G320
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number2 40-2
StatePublished - 1999


  • Amylase
  • Neurokinin receptors
  • Pancreatic juice
  • Sensory nerves
  • Tachykinins

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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