| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
HORMONES AND SIGNALING
Departments of 1Molecular and Integrative Physiology and 2Internal Medicine, The University of Michigan Medical School, Ann Arbor, Michigan 48109-0622; and 3Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710
Submitted 16 October 2003 ; accepted in final form 15 December 2003
CCK acts on pancreatic acinar cells to increase intracellular Ca2+ leading to secretion of digestive enzymes and, in the long term, pancreatic growth. Calcineurin (CN) is a serine/threonine-specific protein phosphatase activated by Ca2+ and calmodulin that recently has been shown to participate in the growth regulation of cardiac and skeletal myocytes. We therefore tested the effect of two different CN inhibitors, cyclosporine A (CsA) and FK506, on mouse pancreatic growth induced by oral administration of the synthetic protease inhibitor camostat, a known stimulator of endogenous CCK release. Mice were fed a powdered diet with or without 0.1% camostat. Pancreatic wet weight, protein, and DNA were increased in response to camostat in a time-dependent manner over 10 days in ICR mice but not in CCK-deficient mice. Both CsA (15 mg/kg) and FK506 (3 mg/kg) given twice daily blocked the increase in pancreatic wet weight and protein and DNA content induced by camostat. The increase in plasma CCK induced by camostat was not blocked by CsA or FK506. Camostat feeding also increased the relative amount of CN protein, whereas levels of MAPKs, ERKs, and p38 were not altered. In summary, 1) CCK released by chronic camostat feeding induces pancreatic growth in mice; 2) this growth is blocked by treatment with both CsA and FK506, indicating a role for CN; 3) CCK stimulation also increases CN protein. In conclusion, activation and possibly upregulation of CN may participate in regulation of pancreatic growth by CCK in mice.
cholecystokinin; camostat; FK506; cyclosporine A
This article has been cited by other articles:
|
|
 |
|
  S. J. Crozier, M. D. Sans, C. H. Lang, L. G. D'Alecy, S. A. Ernst, and J. A. Williams CCK-induced pancreatic growth is not limited by mitogenic capacity in mice Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1148 - G1157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. T. Gurda, L. Guo, S.-H. Lee, J. D. Molkentin, and J. A. Williams Cholecystokinin Activates Pancreatic Calcineurin-NFAT Signaling In Vitro and In Vivo Mol. Biol. Cell, January 1, 2008; 19(1): 198 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Z. Husain, W. M. Grant, F. S. Gorelick, M. H. Nathanson, and A. U. Shah Caerulein-induced intracellular pancreatic zymogen activation is dependent on calcineurin Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1594 - G1599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Guo, M. D. Sans, G. T. Gurda, S.-H. Lee, S. A. Ernst, and J. A. Williams Induction of early response genes in trypsin inhibitor-induced pancreatic growth Am J Physiol Gastrointest Liver Physiol, February 1, 2007; 292(2): G667 - G677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Crozier, M. D. Sans, L. Guo, L. G. D'Alecy, and J. A. Williams Activation of the mTOR signalling pathway is required for pancreatic growth in protease-inhibitor-fed mice J. Physiol., June 15, 2006; 573(3): 775 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Kloting, N. Follak, and I. Kloting Is there an autoimmune process in bone? Gene expression studies in diabetic and nondiabetic BB rats as well as BB rat-related and -unrelated rat strains Physiol Genomics, December 14, 2005; 24(1): 59 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Sans and J. A. Williams Calcineurin is required for translational control of protein synthesis in rat pancreatic acini Am J Physiol Cell Physiol, August 1, 2004; 287(2): C310 - C319. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
