Abstract
The effect of glucocorticoids on the regulation of the substance P receptor (SPR) mRNA was studied in rat pancreatic acinar AR42J cells by Northern blot analysis with the cloned cDNA. After a lag period of about 1 h, dexamethasone rapidly decreased steady-state SPR mRNA to almost negligible levels by 2 h. This decrease occurred in a dose-dependent manner by dexamethasone and was caused by various steroids in accordance with their relative potencies as glucocorticoids. These results indicate that the expression of the SPR mRNA is selectively and negatively regulated by glucocorticoids through interaction with the glucocorticoid receptor. The mechanisms of reduction of SPR mRNA levels were studied by treatment of AR42J cells with actinomycin D or cycloheximide. The SPR mRNA half-life was approximately 30 min, and this rate remained unchanged by dexamethasone treatment. Furthermore, the rapid turnover of the SPR mRNA required ongoing protein synthesis. On the basis of the result of actinomycin D treatment, together with kinetics of dexamethasone-induced changes in SPR mRNA levels, we discuss the mechanism in which glucocorticoids act at transcription initiation to reduce SPR mRNA levels.
Highlights
Selective Inhibition of Expression of the Substance P Receptor mRNA in Pancreatic Acinar AR42J Cells by Glucocorticoids*
The observed decrease in substance P receptor (SPR) mRNA levels after prolonged incubation of cycloheximide was probably due to the cytotoxic effect of cycloheximide on AR42J cells, because the concentration of cycloheximide used was found to inhibit more than 95% of AR42J cell protein synthesis
We showed that dexamethasone has a marked effect on the expression of the SPR mRNA in AR42J cells, leading to an almost complete disappearance of the mRNA within 3-h treatment
Summary
The effect of glucocorticoids on the regulation of the substance P receptor (SPR) mRNA was studied in rat pancreatic acinar AR42J cells by Northern blot analysis with the cloned cDNA. SPR mRNA to almost negligible levels by 2 h This decrease occurred in a dose-dependent manner by dexamethasone and was caused by various steroids in accordance with their relative potencies as glucocorticoids. These results indicate that the expression of the SPR mRNA is selectively and negatively regulated by glucocorticoids through interaction with the glucocorticoid receptor. We report that glucocorticoids selectively inhibit the expression of the SPR gene in the rat pancreatic acinar cell line AR42J
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