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Continuous infusion of cholecystokinin leads to down-regulation of the cholecystokinin-A receptor in the rat pancreas

Ohlsson, Bodil LU ; Borg, K; Mulder, H; Rehfeld, J F; Axelson, J and Sundler, F (2000) In Scandinavian Journal of Gastroenterology 35(6). p.612-618
Abstract
BACKGROUND: Infusion of sulphated cholecystokinin-8 (CCK-8S) in rats transiently increased the proliferation of pancreatic acinar cells, whereas the CCK-A receptor antagonist devazepide decreased such proliferation. This effect ceased after 3 days. CCK-8S or devazepide injected twice daily induced a persistent effect on the cell proliferation involving the major cells of the exocrine pancreas. The aim of this study was to examine the effect of continuous infusion of CCK-8S and devazepide on CCK-A receptor gene expression. METHODS: Male Sprague-Dawley rats received subcutaneous continuous infusion of 5 microg/kg/h CCK-8S, 200 microg/kg/h devazepide, or 1% bovine serum albumin (BSA) by means of osmotic minipumps. The rats were killed after 4... (More)
BACKGROUND: Infusion of sulphated cholecystokinin-8 (CCK-8S) in rats transiently increased the proliferation of pancreatic acinar cells, whereas the CCK-A receptor antagonist devazepide decreased such proliferation. This effect ceased after 3 days. CCK-8S or devazepide injected twice daily induced a persistent effect on the cell proliferation involving the major cells of the exocrine pancreas. The aim of this study was to examine the effect of continuous infusion of CCK-8S and devazepide on CCK-A receptor gene expression. METHODS: Male Sprague-Dawley rats received subcutaneous continuous infusion of 5 microg/kg/h CCK-8S, 200 microg/kg/h devazepide, or 1% bovine serum albumin (BSA) by means of osmotic minipumps. The rats were killed after 4 days; I h before being killed they received 5-bromo-2-deoxyuridine (BrdU) intraperitoneally. Plasma was collected for analysis of CCK. The pancreas was dissected, and indirect immunofluorescence for BrdU and CCK-A receptor was performed. In situ hybridization to CCK-A receptor mRNA was performed for examination and semiquantification of receptor gene expression. RESULTS: Continuous infusion of CCK-8S led to a sixfold increase in plasma CCK and a 40% increase in pancreatic weight. Devazepide did not affect the CCK level but decreased the pancreatic weight by 24% compared with BSA-infused rats. The BrdU labeling indicated that CCK-8S had no effect on cell proliferation. Immunofluorescence for the CCK-A receptor showed a decreased labeling intensity after CCK-8S infusion. The mean optical density of in situ hybridization labeling of the sections from CCK-8S-treated rats was decreased to 37% +/- 3% of that in controls. Devazepide did not affect the CCK-A receptor gene expression. CONCLUSIONS: Continuous stimulation of the CCK-A receptor led to a downregulation of the receptor gene expression in pancreatic acinar cells and decreased labeling of the receptor at immunohistochemistry. The results suggest that down-regulation of the receptor is a protective mechanism against overstimulation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cholecystokinin, cholecystokinin-A receptor, pancreas, receptor regulation
in
Scandinavian Journal of Gastroenterology
volume
35
issue
6
pages
612 - 618
publisher
Taylor & Francis
external identifiers
  • pmid:10912661
  • scopus:0033938932
ISSN
1502-7708
DOI
10.1080/003655200750023570
language
English
LU publication?
yes
id
360e4358-3ec1-4a37-ad5a-b14078c01eb5 (old id 1116697)
date added to LUP
2008-07-01 15:35:20
date last changed
2017-01-01 07:22:28
@article{360e4358-3ec1-4a37-ad5a-b14078c01eb5,
  abstract     = {BACKGROUND: Infusion of sulphated cholecystokinin-8 (CCK-8S) in rats transiently increased the proliferation of pancreatic acinar cells, whereas the CCK-A receptor antagonist devazepide decreased such proliferation. This effect ceased after 3 days. CCK-8S or devazepide injected twice daily induced a persistent effect on the cell proliferation involving the major cells of the exocrine pancreas. The aim of this study was to examine the effect of continuous infusion of CCK-8S and devazepide on CCK-A receptor gene expression. METHODS: Male Sprague-Dawley rats received subcutaneous continuous infusion of 5 microg/kg/h CCK-8S, 200 microg/kg/h devazepide, or 1% bovine serum albumin (BSA) by means of osmotic minipumps. The rats were killed after 4 days; I h before being killed they received 5-bromo-2-deoxyuridine (BrdU) intraperitoneally. Plasma was collected for analysis of CCK. The pancreas was dissected, and indirect immunofluorescence for BrdU and CCK-A receptor was performed. In situ hybridization to CCK-A receptor mRNA was performed for examination and semiquantification of receptor gene expression. RESULTS: Continuous infusion of CCK-8S led to a sixfold increase in plasma CCK and a 40% increase in pancreatic weight. Devazepide did not affect the CCK level but decreased the pancreatic weight by 24% compared with BSA-infused rats. The BrdU labeling indicated that CCK-8S had no effect on cell proliferation. Immunofluorescence for the CCK-A receptor showed a decreased labeling intensity after CCK-8S infusion. The mean optical density of in situ hybridization labeling of the sections from CCK-8S-treated rats was decreased to 37% +/- 3% of that in controls. Devazepide did not affect the CCK-A receptor gene expression. CONCLUSIONS: Continuous stimulation of the CCK-A receptor led to a downregulation of the receptor gene expression in pancreatic acinar cells and decreased labeling of the receptor at immunohistochemistry. The results suggest that down-regulation of the receptor is a protective mechanism against overstimulation.},
  author       = {Ohlsson, Bodil and Borg, K and Mulder, H and Rehfeld, J F and Axelson, J and Sundler, F},
  issn         = {1502-7708},
  keyword      = {Cholecystokinin,cholecystokinin-A receptor,pancreas,receptor regulation},
  language     = {eng},
  number       = {6},
  pages        = {612--618},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Gastroenterology},
  title        = {Continuous infusion of cholecystokinin leads to down-regulation of the cholecystokinin-A receptor in the rat pancreas},
  url          = {http://dx.doi.org/10.1080/003655200750023570},
  volume       = {35},
  year         = {2000},
}