DIFFERENTIAL DOWN-REGULATION OF PULMONARY BETA-1-ADRENOCEPTOR AND BETA-2-ADRENOCEPTOR MESSENGER-RNA WITH PROLONGED IN-VIVO INFUSION OF ISOPRENALINE

The down-regulation by isoprenaline of beta1 and beta2-adrenoceptors in rat lung was investigated at the receptor protein and messenger RNA level. Rats were treated with either isoprenaline or vehicle for 2 h, 1 day and 7 days. Isoprenaline treatment resulted in significant decreases of both beta1- and beta2-adrenoceptor density after 1 day with maximal decreases of 65 +/- 7 and 65 +/- 5% for beta1- and beta2-adrenoceptors, respectively, at 7 days. The administration of isoprenaline had no effect on binding affinities of either beta1 or beta2-adrenoceptors. Beta1-adrenoceptor mRNA was significantly decreased by 58 +/- 10, 73 +/- 4 and 51 +/- 11 % at 2 h, 1 day and 7 days, respectively, after isoprenaline treatment. However, the beta2-adrenoceptor mRNA was not changed at 2 h after treatment and was significantly decreased by 35 +/- 11 and 45 +/- 12% at 1 day and 7 days, respectively after treatment. This time course of beta2-adrenoceptor mRNA correlated well with that of the transcription factor cyclic AMP response element binding protein-like DNA binding activity, determined by gel shift assay. These findings indicate the existence of distinct mechanisms for down-regulation of beta1- and beta2-adrenoceptors and suggest the involvement of cyclic AMP response element binding protein in the down-regulation of beta2-adrenoceptors in rat lung.