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

doi:10.1152/ajpgi.1999.277.2.g314

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

Molecular Pathobiology

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English (US)
Pages (from-to)	G314-G320
Journal	American Journal of Physiology - Gastrointestinal and Liver Physiology
Volume	277
Issue number	2 40-2
DOIs	https://doi.org/10.1152/ajpgi.1999.277.2.g314
State	Published - 1999

Keywords

Amylase
Neurokinin receptors
Pancreatic juice
Sensory nerves
Tachykinins

ASJC Scopus subject areas

Physiology
Hepatology
Gastroenterology
Physiology (medical)

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10.1152/ajpgi.1999.277.2.g314

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title = "Substance P inhibits pancreatic exocrine secretion via a neural mechanism",

abstract = "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.",

keywords = "Amylase, Neurokinin receptors, Pancreatic juice, Sensory nerves, Tachykinins",

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

year = "1999",

doi = "10.1152/ajpgi.1999.277.2.g314",

language = "English (US)",

volume = "277",

pages = "G314--G320",

journal = "American Journal of Physiology - Gastrointestinal and Liver Physiology",

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AU - Kirkwood, Kimberly S.

AU - Kim, Edward H.

AU - He, Xiao Dong

AU - Calaustro, Edna Q.

AU - Domush, Christopher

AU - Yoshimi, Shandra K.

AU - Grady, Eileen F.

AU - Maa, John

AU - Bunnett, Nigel W.

AU - Debas, Haile T.

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

KW - Amylase

KW - Neurokinin receptors

KW - Pancreatic juice

KW - Sensory nerves

KW - Tachykinins

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SN - 0193-1857

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JO - American Journal of Physiology - Gastrointestinal and Liver Physiology

JF - American Journal of Physiology - Gastrointestinal and Liver Physiology

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ER -

Substance P inhibits pancreatic exocrine secretion via a neural mechanism

Abstract

Keywords

ASJC Scopus subject areas

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