Agonist-induced down-regulation of the β2-adrenoceptor and its mRNA in human mononuclear leukocytes
| Autor: | Dieter Ratge, Viola Tittelbach, Jean-Nicolas Volff, Jeanette Giray, Hermann Wisser |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Agonist Transcription Genetic medicine.drug_class Down-Regulation Biology Polymerase Chain Reaction Sensitivity and Specificity Biochemistry Peripheral blood mononuclear cell Andrology Downregulation and upregulation Reference Values Isoprenaline medicine Humans RNA Messenger Receptor Adrenergic beta-2 Receptor Agonists Incubation Pharmacology Messenger RNA Isoproterenol Adrenergic beta-Agonists Mechanism of action Leukocytes Mononuclear medicine.symptom Half-Life medicine.drug |
| Zdroj: | Biochemical Pharmacology. 56:967-975 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/s0006-2952(98)00231-7 |
| Popis: | Agonist-mediated regulation of beta2-adrenoceptors in mononuclear leukocytes has been examined at the protein but not at the mRNA level. In the present study, incubation of mononuclear leukocytes with the beta-agonist (-)-isoproterenol (10(-6) M) for up to 42 hr led to a maximum decrease in both beta2-adrenoceptor mRNA concentration and total receptor number of ca. 56 and 70%, respectively. The decrease in the mRNA level, however, was slower than for the protein level. After 4 hr of incubation with the beta-agonist, the protein level decreased to a minimum of 65% of the initial amount, while an incubation of 8 hr was necessary to reach a similar decrease in the level of mRNA (69% of the initial level). Measurements of mRNA stability revealed a reduction in the half-life of beta2-adrenoceptor mRNA from 2.7 to 1.1 hr following 4 hr of incubation with (-)-isoproterenol. Our data clearly demonstrate that treatment of human mononuclear leukocytes with (-)-isoproterenol induces a beta2-adrenoceptor down-regulation together with a slower time course of mRNA down-regulation which is partly due to a reduction of mRNA stability. |
| Databáze: | OpenAIRE |
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