AJP - Gastrointestinal and Liver Physiology, Vol 267, Issue 5 772-G777, Copyright © 1994 by American Physiological Society
Transient stabilization of cholecystokinin A receptor mRNA by glucocorticoids in pancreatic AR42J cells
S. Rosewicz, E. O. Riecken and A. Kaiser
Department of Gastroenterology, Medizinische Klinik und Poliklinik, Klinikum Steglitz, Freie Universitat Berlin, Germany.
We have characterized the effects of glucocorticoids on gene expression of
the cholecystokinin A receptor (CCK-R) using a cloned cDNA probe in the rat
pancreatic acinar cell line AR42J. Dexamethasone (100 nM) resulted in a
transient, time-dependent increase of CCK-R mRNA, with a maximal induction
observed after 3 h of hormone treatment (238 +/- 29% of controls, n = 4).
Further incubation with dexamethasone resulted in a subsequent decrease of
CCK-R mRNA concentrations, which reached control values after 12 h of
hormonal treatment. The increase of CCK-R mRNA was dose dependent with
half-maximal effects observed at 10 nM and maximal effects observed at 100
nM of hormone. We next investigated the molecular mechanisms by which
glucocorticoids induce CCK-R gene expression. Nuclear run-on analysis
revealed that dexamethasone pretreatment had no significant effect on CCK-R
gene transcription. Using actinomycin D, we determined the half-life for
the mRNA of the CCK-R. Dexamethasone (100 nM) pretreatment for 3 h resulted
in a significant increase of CCK-R mRNA stability, with a half-life of 240
min compared with 120 min in untreated control cells. These data therefore
suggest that glucocorticoids transiently stimulate CCK-R mRNA
concentrations by increasing the mRNA stability without affecting the
receptor transcription rate.
