β‐Adrenergic Receptors in Brown‐Adipose Tissue. Characterization and Alteratios during Acclimation of Rats to Cold

Binding of (−)‐[³H]dihydroalprenolol to unfractionated membranes was rapid, stable, saturable and reversible. It displayed the affinity, specificity and stereoselectivity expected of binding to adenylate cyclase‐coupled β‐adrenergic receptors. β‐Adrenergic agonists competed for binding sites with an order of potency typical of the β1 subtype of adrenergic receptors: (−)‐Isoproterenol > (−)‐norepinephrine ≥ (−)‐epinephrine. Binding exhibited a remarkable stereoselectivity, the (−)‐isomers of β‐adrenergic agonists and antagonists being 34 to 280 times more potent than the (+)‐isomers in competing for (−)‐[³H]dihydroalprenolol binding sites.

Total interscapular brown adipose tissue of the adult, warm‐acclimated rat contained 1.12 ± 0.08 pmol of (−)‐[³H]dihydroalprenolol binding sites. During cold‐acclimation, growth of the tissue was accompanied by a 4–5‐fold increase in the total number of recptor sites. However, this increase did not keep pace with the increse in brown adipose tissue cellularity (as estimated by total tissue DNA content), resulting in a 40–50% reduction in receptor density. The decrease in receptor density was associated with cold‐exposure rather than with cold‐acclimation.

The affinity of (−)‐[³H]dihydroalprenolol receptor sites was not significantly altered by cold‐acclimation.

The results of this study are interpreted as indicating that catecholamines released via activation of the sympathetic nervous system regulate both the density and the number of their own receptors in brown adipose tissue of cold‐exposed animals. The development of the hyperadrenergic response of this thermogenic tissue during cold‐acclimation may result from a marked organ hyperplasia associated with an increased number of β‐adrenergic receptor sites and cannot be explained by alterations in receptor density or affinity.