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Bombesin receptor gene expression in rat pancreatic acinar AR42J cells: transcriptional regulation by glucocorticoids

Item Type:Article
Title:Bombesin receptor gene expression in rat pancreatic acinar AR42J cells: transcriptional regulation by glucocorticoids
Creators Name:Rosewicz, S. and Detjen, K. and Kaiser, A. and Prosenc, N. and Cervos-Navarro, J. and Riecken, E.O. and Haller, H.
Abstract:BACKGROUND/AIMS: This study investigated the correlation between glucocorticoid-regulated gene expression of the bombesin receptor (BR) and cellular sensitivity to bombesin stimulation in the rat pancreatic acinar cell line AR42J. METHODS: BR gene expression was assessed using a cloned complementary DNA probe and radioligand binding assays. Intracellular Ca2+ mobilization was assessed by dual wavelength spectrophotometry using fura-2 in single cells. RESULTS: Dexamethasone resulted in a rapid dose- and time-dependent decrease of BR messenger RNA levels with maximal inhibition to 25% +/- 2% of controls (n = 4) after 6 hours of hormone treatment. BR messenger RNA half-life was approximately 120 minutes and was not affected by dexamethasone pretreatment; nuclear run-on analysis showed a decreased transcription rate of the BR to approximately 25% of control after hormonal treatment. Radioligand binding studies showed a time-dependent decrease of specific bombesin binding to 25% +/- 8% of control after 48 hours of hormone treatment. Down-regulation of BR gene expression by dexamethasone resulted in a time- and dose-dependent decrease of intracellular Ca2+ mobilization after bombesin stimulation compared with untreated controls. CONCLUSIONS: Glucocorticoids decrease BR gene transcription. The subsequent decrease in cellular BR number renders AR42J cells less sensitive for bombesin-stimulated intracellular Ca2+ mobilization.
Keywords:Bombesin, Calcium, Cell Line, Dexamethasone, Down-Regulation, Drug Dose-Response Relationship, Gene Expression Regulation, Glucocorticoids, Iodine Radioisotopes, Pancreas, Messenger RNA, Bombesin Receptors, Glucocorticoid Receptors, Time Factors, Genetic Transcription, Animals, Rats
Page Range:208-218
Date:July 1994
PubMed:View item in PubMed

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