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.
authors.affiliation: Departments of Surgery and Physiology, University of California School of Medicine, San Francisco, California 94143, USA. ksk@itsa.ucsf.edu
authors.forename: K S
authors.initials: KS
authors.lastname: Kirkwood
authors.forename: E H
authors.initials: EH
authors.lastname: Kim
authors.forename: X D
authors.initials: XD
authors.lastname: He
authors.forename: E Q
authors.initials: EQ
authors.lastname: Calaustro
authors.forename: C
authors.initials: C
authors.lastname: Domush
authors.forename: S K
authors.initials: SK
authors.lastname: Yoshimi
authors.forename: E F
authors.initials: EF
authors.lastname: Grady
authors.forename: J
authors.initials: J
authors.lastname: Maa
authors.forename: N W
authors.initials: NW
authors.lastname: Bunnett
authors.forename: H T
authors.initials: HT
authors.lastname: Debas
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D008297:Male; D009407:Nerve Block; D009424:Nervous System Physiological Phenomena / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010179:Pancreas / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D018040:Receptors, Neurokinin-1; D013373:Substance P; D013779:Tetrodotoxin; D001285:Atropine; D002211:Capsaicin