Cold exposure regulates the norepinephrine uptake transporter in rat brownadipose tissue

The neuronal uptake of norepinephrine (NE) in sympathetically innervated ti ssues is mediated by a high-affinity NE uptake transporter (NET). Rat inter scapular brown adipose tissue (ISBAT) is densely innervated by the sympathe tic nervous system for the control of cold- and diet-induced thermogenesis. To determine if cold exposure regulates the NET, kinetic parameters for [H -3]NE uptake and [H-3]nisoxetine (Nis) binding were determined in ISBAT fro m 7-day cold-exposed (CE) and control rats. Uptake of [H-3]NE in ISBAT slic es was of high affinity (1.6 mu M). After 7 days of cold exposure the affin ity for [H-3]NE uptake was not altered; however, the uptake capacity was de creased (38%) in ISBAT slices from CE rats. Kinetic parameters for [H-3]Nis binding demonstrated a single high-affinity site in ISBAT from CE and cont rol rats with similar affinity. The density of [H-3]Nis sites in ISBAT was decreased (38%) following cold exposure. A time course (2 h-7 days) for col d exposure demonstrated downregulation of [H-3]Nis binding density by day 3 , which remained through day 7. The affinity for [H-3]Nis binding was trans iently decreased at 2 h of cold exposure. Similarly, ISBAT NE content was d ecreased at 2 h of cold exposure. Pair feeding CE rats to food intake of co ntrols normalized plasma NE content; however, [H-3]Nis binding density in I SBAT remained decreased in pair-fed rats. These results demonstrate that th e ISBAT NET is downregulated following cold exposure. Reductions in ISBAT N E content precede alterations in NET density; however, plasma NE content is not related to regulation of the NET.