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The effect of intermittent injections of CCK-8S and the CCK-A receptor antagonist devazepide on cell proliferation in exocrine rat pancreas

Ohlsson, Bodil LU ; Borg, Karin; Rehfeld, J F; Ihse, Ingemar LU and Axelson, Jan LU (1998) In International Journal of Pancreatology 24(3). p.211-218
Abstract
CONCLUSION: Intermittent injections of sulfated cholecystokinin-8 (CCK-8S) or devazepide caused long-lasting effects on cell proliferation in exocrine pancreas in contrast to continuous infusion. The acinar cells responded to both treatments with changes in the labeling index (LI) during the whole study period. When studying the influence of stimulation and inhibition of the CCK-A receptor on cell proliferation in the exocrine pancreas, not only are the drugs and doses of importance but also the mode of administration. BACKGROUND: Continuous infusion of CCK-8S or the CCK-A receptor antagonist devazepide induces transient changes in acinar cell proliferation in rat pancreas. The aim of the present experiments was to study whether... (More)
CONCLUSION: Intermittent injections of sulfated cholecystokinin-8 (CCK-8S) or devazepide caused long-lasting effects on cell proliferation in exocrine pancreas in contrast to continuous infusion. The acinar cells responded to both treatments with changes in the labeling index (LI) during the whole study period. When studying the influence of stimulation and inhibition of the CCK-A receptor on cell proliferation in the exocrine pancreas, not only are the drugs and doses of importance but also the mode of administration. BACKGROUND: Continuous infusion of CCK-8S or the CCK-A receptor antagonist devazepide induces transient changes in acinar cell proliferation in rat pancreas. The aim of the present experiments was to study whether intermittent administration of CCK-8S or devazepide prevents receptor desensitization and thereby affects exocrine pancreatic cell proliferation persistently. METHODS: Male Sprague-Dawley rats were injected subcutaneously twice daily with CCK-8S (6 micrograms), devazepide (240 micrograms) or bovine serum albumin (BSA). The rats were sacrificed after 18 and 36 h and 3 and 7 d. One hour before sacrifice, the rats were injected intraperitoneally with 1 mCi/kg of tritiated thymidine. The pancreatic weight and the contents of water, protein, and DNA were determined. The LI (number of labeled cells/100 cells) of exocrine pancreatic cells was determined microscopically after autoradiography. RESULTS: The concentration of plasma CCK was slightly increased by devazepide, but the increase was more pronounced by CCK-8S. The pancreatic wet weight was transiently increased 18 h after the start of CCK-8S injections (+14%), whereas devazepide caused a reduction after 7 d (-22%). The protein content was uninfluenced and the DNA content was decreased at 36 h with either treatment. CCK-8S increased the LI in acinar and centroacinar cells throughout the study period, but the ductal cell LI was increased only after 18 and 36 h. Injection of devazepide was followed by decreased LI of acinar cells throughout the study period. Also, the centroacinar and ductal cell LI decreased initially but returned to control values after 7 d. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cell proliferation, cholecystokinin, intermittent injections, pancreas
in
International Journal of Pancreatology
volume
24
issue
3
pages
211 - 218
publisher
Humana Press
external identifiers
  • pmid:9873956
  • scopus:0032422681
ISSN
0169-4197
DOI
10.1007/BF02788424
language
English
LU publication?
yes
id
1ac9ebbb-4afd-4276-b1a5-b1a6d3bd7898 (old id 1113114)
date added to LUP
2008-07-14 12:03:07
date last changed
2017-01-01 06:56:52
@article{1ac9ebbb-4afd-4276-b1a5-b1a6d3bd7898,
  abstract     = {CONCLUSION: Intermittent injections of sulfated cholecystokinin-8 (CCK-8S) or devazepide caused long-lasting effects on cell proliferation in exocrine pancreas in contrast to continuous infusion. The acinar cells responded to both treatments with changes in the labeling index (LI) during the whole study period. When studying the influence of stimulation and inhibition of the CCK-A receptor on cell proliferation in the exocrine pancreas, not only are the drugs and doses of importance but also the mode of administration. BACKGROUND: Continuous infusion of CCK-8S or the CCK-A receptor antagonist devazepide induces transient changes in acinar cell proliferation in rat pancreas. The aim of the present experiments was to study whether intermittent administration of CCK-8S or devazepide prevents receptor desensitization and thereby affects exocrine pancreatic cell proliferation persistently. METHODS: Male Sprague-Dawley rats were injected subcutaneously twice daily with CCK-8S (6 micrograms), devazepide (240 micrograms) or bovine serum albumin (BSA). The rats were sacrificed after 18 and 36 h and 3 and 7 d. One hour before sacrifice, the rats were injected intraperitoneally with 1 mCi/kg of tritiated thymidine. The pancreatic weight and the contents of water, protein, and DNA were determined. The LI (number of labeled cells/100 cells) of exocrine pancreatic cells was determined microscopically after autoradiography. RESULTS: The concentration of plasma CCK was slightly increased by devazepide, but the increase was more pronounced by CCK-8S. The pancreatic wet weight was transiently increased 18 h after the start of CCK-8S injections (+14%), whereas devazepide caused a reduction after 7 d (-22%). The protein content was uninfluenced and the DNA content was decreased at 36 h with either treatment. CCK-8S increased the LI in acinar and centroacinar cells throughout the study period, but the ductal cell LI was increased only after 18 and 36 h. Injection of devazepide was followed by decreased LI of acinar cells throughout the study period. Also, the centroacinar and ductal cell LI decreased initially but returned to control values after 7 d.},
  author       = {Ohlsson, Bodil and Borg, Karin and Rehfeld, J F and Ihse, Ingemar and Axelson, Jan},
  issn         = {0169-4197},
  keyword      = {Cell proliferation,cholecystokinin,intermittent injections,pancreas},
  language     = {eng},
  number       = {3},
  pages        = {211--218},
  publisher    = {Humana Press},
  series       = {International Journal of Pancreatology},
  title        = {The effect of intermittent injections of CCK-8S and the CCK-A receptor antagonist devazepide on cell proliferation in exocrine rat pancreas},
  url          = {http://dx.doi.org/10.1007/BF02788424},
  volume       = {24},
  year         = {1998},
}