Objective: Corticotropin-releasing factor receptor type 2 (CRF R2) messenger RNA (mRNA) expression in the rodent heart or vessels is modulated by exposure to urocortin and glucocorticoids. In addition, we previously found that incubation with a variety of cytokines, such as interleukin (IL)-1 and IL-6, and tumor necrosis factor-α also reduced CRF R2β mRNA expression, with IL-1β being the most effective. In this study, we further explored the regulation of CRF R2β mRNA levels by IL-1β in the rat vascular smooth muscle A7r5 cells. Methods: A7r5 cells were incubated with IL-1β, urocortin, or both for 6 h, after pre-incubating with or without anti-IL-1β antibody (Ab) for 30 min, and then CRF R2β mRNA levels were measured by RNase protection assay. Cells were incubated with lipopolysaccharides, IL-1β, IL-6 , dexamethasone, forskolin, or urocortin for 20 min, and then intracellular cAMP was measured by cAMP RIA. Results: IL-1β produced a significant time-dependent decrease in CRF R2β mRNA levels. Combined urocortin and IL-1β administration did not have synergistic effects on the decrease in CRF R2β mRNA levels. IL-1β Ab failed to block the ability of urocortin to regulate CRF R2β mRNA levels, suggesting that urocortin regulated CRF R2β mRNA levels via another pathway than IL-1β production. Urocortin induced the intracellular cAMP production in A7r5 cells, while IL-1β failed to induce it. Conclusion: The multifactorial regulation of CRF R2β mRNA expression in the A7r5 cells serves to limit the inotropic and chronotropic effects of CRF R2 agonists such as urocortin during prolonged physical or immune challenge.

Keywords:
Aorta, Corticotropin-releasing factor receptor, Cytokines, Glucocorticoids, Hypothalamus-pituitary-adrenal axis, Immune system, Lipopolysaccharides, Stress, Urocortin
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© 2002 S. Karger AG, Basel
2002
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