Long-term exposure to norepinephrine results in down-regulation and reduced mRNA expression of pulmonary beta-adrenergic receptors in guinea pigs

Am J Respir Cell Mol Biol. 1994 Jan;10(1):91-9. doi: 10.1165/ajrcmb.10.1.8292387.

Abstract

We studied the down-regulation of beta 2-adrenoceptors in guinea pig lung after chronic exposure to a beta-agonist. Guinea pigs were exposed to either norepinephrine (NE) or vehicle for 7 days. The density and affinity of beta-adrenoceptors were determined by Scatchard analysis of [125I]cyanopindolol binding in a lung membrane preparation and beta 1- and beta 2-adrenoceptor subtypes were studied in the presence of 0.1 microM ICI 118,551, a selective beta 2-adrenoceptor antagonist, or 0.1 microM CGP 20712 A, a selective beta 1-adrenoceptor antagonist, respectively. beta 2-Adrenoceptor mRNA was examined by Northern blot analysis. The tissue distribution of beta 2-adrenoceptors and of beta 2-adrenoceptor mRNA in lung after NE infusion were determined using receptor autoradiography and in situ hybridization, respectively. The functional significance of the decrease in beta 2-adrenoceptor was tested by measuring the relaxation response to a beta 2-agonist in isolated parenchymal strips. NE treatment resulted in decreases of 75 +/- 9%, 84 +/- 4%, and 66 +/- 9% of total beta-, beta 1-, and beta 2-adrenoceptors in the lung, compared with control animals. The administration of NE had only minimal effects on the dissociation constant (Kd) of the receptor for the radioligand. beta 2-Adrenoceptors mRNA was decreased by 46 +/- 13% after NE treatment. There was a correspondence between the distribution of beta 2-adrenoceptors and beta 2-adrenoceptor mRNA localization in both control and NE-treated guinea pigs. NE treatment reduced alveolar beta 2-adrenoceptors by 70 +/- 3% and its mRNA expression by 78 +/- 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

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

MeSH terms

  • Animals
  • Blotting, Northern
  • Down-Regulation
  • Guinea Pigs
  • In Situ Hybridization
  • In Vitro Techniques
  • Lung / drug effects*
  • Lung / metabolism
  • Male
  • Norepinephrine / pharmacology*
  • RNA, Messenger / drug effects*
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic, beta-1 / drug effects*
  • Receptors, Adrenergic, beta-1 / metabolism
  • Receptors, Adrenergic, beta-2 / drug effects*
  • Receptors, Adrenergic, beta-2 / metabolism
  • Time Factors

Substances

  • RNA, Messenger
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Norepinephrine