Cell type-specific regulation of beta(2)-adrenoceptor mRNA by agonists

Prolonged agonist stimulation of beta(2)-adrenoceptors results in receptor down-regulation which is often paralleled by a reduction of the corresponding mRNA. In this study, we investigated the agonist-dependent regulation of beta(2)-adrenoceptor mRNA in DDT1-MF2 smooth muscle cells and C6 glioma cells. In DDT1-MF2 cells the half-life of the mRNA was 12 h in monolayer compared to 2 h in suspension cultures. Under both conditions, the agonist isoproterenol reduced this half-life by a factor of 2. In contrast, in C6 glioma cells isoproterenol had no effect on the mRNA stability, even though it reduced mRNA levels by approximate to 50%. Isoproterenol-induced downregulation of beta(2)-adrenoceptor mRNA was completely blocked in C6 cells by the presence of a protein synthesis inhibitor, while this was not so in DDT1-MF2-cells. These data show that beta(2)-adrenoceptor downregulation occurs via cell-type specific mechanisms. (C) 1997 Elsevier Science B.V.