CCK-B receptor antagonist YF476 inhibits pancreatic enzyme secretion at a duodenal level in pigs
(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:
https://lup.lub.lu.se/record/267240
- author
- Evilevitch, Lena LU ; Weström, Björn LU and Pierzynowski, Stefan LU
- organization
- publishing date
- 2004
- 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
- 2016-04-01 17:06:45
- date last changed
- 2022-01-29 00:28:21
@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}}, keywords = {{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}}, doi = {{10.1080/00365520410006242}}, volume = {{39}}, year = {{2004}}, }