Differential down-regulation of pulmonary beta 1- and beta 2-adrenoceptor messenger RNA with prolonged in vivo infusion of isoprenaline

Eur J Pharmacol. 1993 Oct 15;247(2):131-8. doi: 10.1016/0922-4106(93)90070-p.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cyclic AMP / biosynthesis
  • Down-Regulation / drug effects*
  • Infusions, Intravenous
  • Isoproterenol / administration & dosage
  • Isoproterenol / pharmacology*
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-1 / biosynthesis*
  • Receptors, Adrenergic, beta-1 / drug effects
  • Receptors, Adrenergic, beta-2 / biosynthesis*
  • Receptors, Adrenergic, beta-2 / drug effects
  • Transcription Factors / biosynthesis

Substances

  • RNA, Messenger
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Transcription Factors
  • Cyclic AMP
  • Isoproterenol