Cell type-specific regulation of beta2-adrenoceptor mRNA by agonists.
Prolonged agonist stimulation of beta2-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 beta2-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 approximately 50%. Isoproterenol-induced downregulation of beta2-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 beta2-adrenoceptor downregulation occurs via cell-type specific mechanisms.
Danner
S
S
Institute of Pharmacology, University of Würzburg, Germany.
Lohse
M J
MJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D002453:Cell Cycle; D002460:Cell Line; D006224:Cricetinae; D015536:Down-Regulation; D005098:Exotoxins / Q000494:pharmacology; D005786:Gene Expression Regulation; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis*; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000318:Adrenergic beta-Agonists; D005098:Exotoxins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol