Bombesin receptor gene expression in rat pancreatic acinar AR42J cells: Transcriptional regulation by glucocorticoids
| Autor: | Nikolaja Prosenc, Jorge Cervos-Navarro, Stefan Rosewicz, Hermann Haller, Katharina Detjen, Ernst-Otto Riecken, A Kaiser |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Time Factors Transcription Genetic medicine.medical_treatment Down-Regulation Peptide hormone Biology Dexamethasone Cell Line Iodine Radioisotopes chemistry.chemical_compound Receptors Glucocorticoid Internal medicine Gene expression Transcriptional regulation medicine Acinar cell Animals RNA Messenger Glucocorticoids Pancreas Messenger RNA Dose-Response Relationship Drug Hepatology Gastroenterology Bombesin Rats Bombesin receptor Receptors Bombesin Steroid hormone Endocrinology Gene Expression Regulation chemistry Calcium |
| Zdroj: | Gastroenterology. 107:208-218 |
| ISSN: | 0016-5085 |
| DOI: | 10.1016/0016-5085(94)90079-5 |
| Popis: | 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 Ca 2+ 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 Ca 2+ 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 Ca 2+ mobilization. |
| Databáze: | OpenAIRE |
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