Advanced

CCK-B receptor antagonist YF476 inhibits pancreatic enzyme secretion at a duodenal level in pigs

Evilevitch, Lena LU ; Weström, Björn LU and Pierzynowski, Stefan LU (2004) In Scandinavian Journal of Gastroenterology 39(9). p.886-890
Abstract
Background: To evaluate the mechanisms by which cholecystokinin (CCK) regulates the exocrine pancreas, the role and location of CCK receptors in the pig were investigated using the CCK-B receptor antagonist YF476 and different administration routes of CCK. Methods: In 11 anaesthetized pigs, catheters were surgically implanted in the pancreatic duct for juice collection, and in the gastric arteries and jugular vein, so that infusions of CCK-33 could be directed to the duodenal/gastric, duodenal/ pancreatic or general circulations, respectively. Experiments were performed under control conditions, and after pretreatment by gavage feeding with YF476, using either a single, low dose of 0.3 mumol kg(-1), which would block the CCK-B receptors,... (More)
Background: To evaluate the mechanisms by which cholecystokinin (CCK) regulates the exocrine pancreas, the role and location of CCK receptors in the pig were investigated using the CCK-B receptor antagonist YF476 and different administration routes of CCK. Methods: In 11 anaesthetized pigs, catheters were surgically implanted in the pancreatic duct for juice collection, and in the gastric arteries and jugular vein, so that infusions of CCK-33 could be directed to the duodenal/gastric, duodenal/ pancreatic or general circulations, respectively. Experiments were performed under control conditions, and after pretreatment by gavage feeding with YF476, using either a single, low dose of 0.3 mumol kg(-1), which would block the CCK-B receptors, or a 1000 times higher dose (300 mumol kg(-1)), which would also block the CCK-A receptors. Results: The increase in the pancreatic output of protein and the enzymes trypsin and amylase observed after the infusion of CCK-33 at 13 pmol kg(-1) to the duodenum/stomach or duodenum/pancreas was inhibited by pretreatment with YF476 at both dosages. In contrast, the increase in protein and enzyme output after the infusion of a supraphysiological dose of CCK-33 (130 pmol kg(-1)) to the general circulation was not affected by pretreatment with low dosage YF476, whereas high dosage YF476 completely inhibited the stimulated secretion. Conclusions: These data indicate that CCK-33 given locally to the duodenum in doses raising CCK to physiological plasma levels stimulates the pancreatic enzyme secretion via duodenal CCK-B receptors. Supra-physiological doses of CCK-33 to the general circulation appeared to affect the pancreatic enzyme secretion via CCK-A receptors located elsewhere than in the pancreatic and duodenal tissue. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
exocrine pancreas, CCK-receptors, entero-pancreatic reflex, pig, trypsin
in
Scandinavian Journal of Gastroenterology
volume
39
issue
9
pages
886 - 890
publisher
Taylor & Francis
external identifiers
  • wos:000223910500013
  • pmid:15513388
  • scopus:4544290724
ISSN
1502-7708
DOI
10.1080/00365520410006242
language
English
LU publication?
yes
id
54e8ee49-f28c-4361-b530-284ed01862b9 (old id 267240)
date added to LUP
2007-10-22 15:16:00
date last changed
2017-01-01 07:24:35
@article{54e8ee49-f28c-4361-b530-284ed01862b9,
  abstract     = {Background: To evaluate the mechanisms by which cholecystokinin (CCK) regulates the exocrine pancreas, the role and location of CCK receptors in the pig were investigated using the CCK-B receptor antagonist YF476 and different administration routes of CCK. Methods: In 11 anaesthetized pigs, catheters were surgically implanted in the pancreatic duct for juice collection, and in the gastric arteries and jugular vein, so that infusions of CCK-33 could be directed to the duodenal/gastric, duodenal/ pancreatic or general circulations, respectively. Experiments were performed under control conditions, and after pretreatment by gavage feeding with YF476, using either a single, low dose of 0.3 mumol kg(-1), which would block the CCK-B receptors, or a 1000 times higher dose (300 mumol kg(-1)), which would also block the CCK-A receptors. Results: The increase in the pancreatic output of protein and the enzymes trypsin and amylase observed after the infusion of CCK-33 at 13 pmol kg(-1) to the duodenum/stomach or duodenum/pancreas was inhibited by pretreatment with YF476 at both dosages. In contrast, the increase in protein and enzyme output after the infusion of a supraphysiological dose of CCK-33 (130 pmol kg(-1)) to the general circulation was not affected by pretreatment with low dosage YF476, whereas high dosage YF476 completely inhibited the stimulated secretion. Conclusions: These data indicate that CCK-33 given locally to the duodenum in doses raising CCK to physiological plasma levels stimulates the pancreatic enzyme secretion via duodenal CCK-B receptors. Supra-physiological doses of CCK-33 to the general circulation appeared to affect the pancreatic enzyme secretion via CCK-A receptors located elsewhere than in the pancreatic and duodenal tissue.},
  author       = {Evilevitch, Lena and Weström, Björn and Pierzynowski, Stefan},
  issn         = {1502-7708},
  keyword      = {exocrine pancreas,CCK-receptors,entero-pancreatic reflex,pig,trypsin},
  language     = {eng},
  number       = {9},
  pages        = {886--890},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Gastroenterology},
  title        = {CCK-B receptor antagonist YF476 inhibits pancreatic enzyme secretion at a duodenal level in pigs},
  url          = {http://dx.doi.org/10.1080/00365520410006242},
  volume       = {39},
  year         = {2004},
}