Differential down-regulation of beta3-adrenergic receptor mRNA and signal transduction by cold exposure in brown adipose tissue of young and senescent rats

Pflugers Arch. 1999 Feb;437(3):479-83. doi: 10.1007/s004240050804.

Abstract

Diminished beta3 adrenergic-stimulated thermogenesis in brown adipose tissue (BAT) in senescent rats is restored by a short period of cold exposure. To investigate if the mechanism of this restoration involves preferential up-regulation of beta3-adrenergic signal transduction in senescent compared with young rats, we examined the steady state levels of beta3-adrenergic receptor messenger ribonucleic acid (beta3AR mRNA) and the dose/response relationship for the activation of adenylyl cyclase by the selective beta3-adrenergic agonist, BRL 37344 in BAT membranes from young and senescent rats with or without 2 days cold exposure at 8 degrees C. beta3AR mRNA declined by 30% with age and by 60% with cold exposure in young rats. In contrast, cold exposure did not down-regulate beta3AR mRNA in senescent rats. BRL 37344-stimulated adenylyl cyclase activity was 38% less in senescent rats and was desensitized by cold exposure decreasing maximum stimulation by 78% and increasing, the dissociation constant 2.5-fold. Cold exposure decreased BRL 37344-stimulated adenylyl cyclase activity to a lesser extent in senescent rats (50%), such that the activity was similar in cold-exposed young and old rats. These data indicate that although cold exposure did not, as we hypothesized, up-regulate beta3-adrenergic signal transduction in the senescent rats, cold exposure preferentially down-regulated beta3AR mRNA and beta3AR-mediated adenylyl cyclase in the young compared with senescent rats.

Publication types

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

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Adipose Tissue, Brown / metabolism*
  • Adrenergic beta-Agonists / pharmacology
  • Aging*
  • Animals
  • Cold Temperature*
  • Colforsin / pharmacology
  • Ethanolamines / pharmacology
  • Gene Expression Regulation*
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Adrenergic, beta / genetics*
  • Receptors, Adrenergic, beta / physiology
  • Signal Transduction*

Substances

  • Adrenergic beta-Agonists
  • Ethanolamines
  • RNA, Messenger
  • Receptors, Adrenergic, beta
  • Colforsin
  • BRL 37344
  • Adenylyl Cyclases