Differential down-regulation of pulmonary beta 1- and beta 2-adrenoceptor messenger RNA with prolonged in vivo infusion of isoprenaline.
The down-regulation by isoprenaline of beta 1 and beta 2-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 beta 1- and beta 2-adrenoceptor density after 1 day with maximal decreases of 65 +/- 7 and 65 +/- 5% for beta 1- and beta 2-adrenoceptors, respectively, at 7 days. The administration of isoprenaline had no effect on binding affinities of either beta 1 or beta 2-adrenoceptors. beta 1-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 beta 2-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 beta 2-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 beta 1- and beta 2-adrenoceptors and suggest the involvement of cyclic AMP response element binding protein in the down-regulation of beta 2-adrenoceptors in rat lung.
Nishikawa
M
M
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Mak
J C
JC
Shirasaki
H
H
Barnes
P J
PJ
D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects*; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis* / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis* / Q000187:drug effects; D014157:Transcription Factors / Q000096:biosynthesis
D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D014157:Transcription Factors; D000242:Cyclic AMP; D007545:Isoproterenol