Agonist-induced down-regulation of the beta2-adrenoceptor and its mRNA in human mononuclear leukocytes.
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.
Tittelbach
V
V
Department of Clinical Pathology, Robert Bosch Hospital, Stuttgart, Germany.
Volff
J N
JN
Giray
J
J
Ratge
D
D
Wisser
H
H
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D015536:Down-Regulation / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D007545:Isoproterenol