REGULATION OF THE BETA(2)-ADRENERGIC RECEPTOR AND ITS MESSENGER-RNA IN THE RAT LUNG BY DEXAMETHASONE

Glucocorticoids increase beta(2)-adrenergic responsiveness and receptor density in the lung, but the underlying mechanisms have not been clearly elucidated. To determine whether changes in beta(2)-adrenergic receptor gene expression are involved in vivo, we measured beta(2)-adrenergic receptor mRNA levels and beta(2)-adrenergic receptor density in lungs from Sprague-Dawley rats treated with a daily injection of dexamethasone (1 mg/kg subcutaneously) for 1, 3, or 7 days. Animals were sacrificed either 2 or 24 h after receiving the last injection. beta(2)-Adrenergic receptor mRNA levels were significantly (p < .05) elevated compared to saline-treated controls in the lungs of animals sacrificed 2 h after dexamethasone injection for 1 day (174 +/- 12%), 3 days (236 +/- 18%), and 7 days (220 +/- 11%). Receptor mRNA levels measured 24 h after dexamethasone injection did not differ significantly from the control group. Induction of beta(2)-adrenergic receptor mRNA by dexamethasone was transient, since no significant cumulative or sustained increase in receptor mRNA levels was observed during the study period. Treatment with dexamethasone increased beta(2)-adrenergic receptor density as expected, but no significant increase in receptor density was detected until 24 h after the third daily injection of dexamethasone, when levels reached 2045 +/- 150 fmol/mg protein compared to 1292 +/- 34 fmol/mg protein in the control group. Receptor density then remained at this elevated level through 7 days of treatment. These results show that dexamethasone up-regulates both the beta(2)-adrenergic receptor and its mRNA in vivo in the lung. The induction of beta(2)-adrenergic receptor mRNA levels indicates that glucocorticoids may regulate receptor density in the lung through modulation of gene expression. However, the difference between the time course of induction for the beta(2)-adrenergic receptor and its mRNA suggests that additional translational or post-translational mechanisms may also be involved.