Cold exposure regulates the norepinephrine uptake transporter in rat brown adipose tissue

Am J Physiol. 1999 Jan;276(1):R143-51. doi: 10.1152/ajpregu.1999.276.1.R143.


The neuronal uptake of norepinephrine (NE) in sympathetically innervated tissues is mediated by a high-affinity NE uptake transporter (NET). Rat interscapular brown adipose tissue (ISBAT) is densely innervated by the sympathetic nervous system for the control of cold- and diet-induced thermogenesis. To determine if cold exposure regulates the NET, kinetic parameters for [3H]NE uptake and [3H]nisoxetine (Nis) binding were determined in ISBAT from 7-day cold-exposed (CE) and control rats. Uptake of [3H]NE in ISBAT slices was of high affinity (1.6 microM). After 7 days of cold exposure the affinity for [3H]NE uptake was not altered; however, the uptake capacity was decreased (38%) in ISBAT slices from CE rats. Kinetic parameters for [3H]Nis binding demonstrated a single high-affinity site in ISBAT from CE and control rats with similar affinity. The density of [3H]Nis sites in ISBAT was decreased (38%) following cold exposure. A time course (2 h-7 days) for cold exposure demonstrated downregulation of [3H]Nis binding density by day 3, which remained through day 7. The affinity for [3H]Nis binding was transiently decreased at 2 h of cold exposure. Similarly, ISBAT NE content was decreased at 2 h of cold exposure. Pair feeding CE rats to food intake of controls normalized plasma NE content; however, [3H]Nis binding density in ISBAT remained decreased in pair-fed rats. These results demonstrate that the ISBAT NET is downregulated following cold exposure. Reductions in ISBAT NE content precede alterations in NET density; however, plasma NE content is not related to regulation of the NET.

Publication types

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

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Carrier Proteins / metabolism*
  • Cold Temperature*
  • Feeding Behavior / physiology
  • Fluoxetine / analogs & derivatives
  • Fluoxetine / pharmacokinetics
  • In Vitro Techniques
  • Kinetics
  • Male
  • Norepinephrine / pharmacokinetics
  • Norepinephrine Plasma Membrane Transport Proteins
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Symporters*
  • Time Factors


  • Carrier Proteins
  • Norepinephrine Plasma Membrane Transport Proteins
  • Slc6a2 protein, rat
  • Symporters
  • Fluoxetine
  • nisoxetine
  • Norepinephrine