DESENSITIZATION OF BETA-ADRENERGIC RESPONSIVENESS INVIVO - DECREASED COUPLING BETWEEN RECEPTORS AND ADENYLATE-CYCLASE IN ISOLATED BROWN-FAT CELLS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 128  (2-3) , 481-488
Abstract
Chronic catecholamine stimulation in vivo of brown adipose tissue during acclimation of hamsters to cold does not result in any alteration of .beta.-adrenergic receptor number or affinity when determined in isolated adipocytes by (-)-[3H]dihydroalprenolol binding. Norepinephrine displacement of (-)-[3H]dihydroalprenolol showed the same Ki [inhibition constant] for both groups. The slope of the displacement curve was shallower for cells from cold-acclimated animals than for controls. cAMP accumulation was stimulated by norepinephrine in cells from both groups of animals, although the dose-response curve for cells from cold-acclimated animals was shifted to the right and the maximum value obtained was < 1/2 of that found in cells from control animals. The slope of the curve was again lower. Other catecholamines stimulated cAMP accumulation with an order of potency in agreement with a response mediated through .beta.1-adrenergic receptors. The dose-response curve for norepinephrine-stimulated O2 consumption was also shifted to the right for cells from cold-acclimated animals, although the maximal respiration was only slightly reduced. The slope factor was again decreased. The results are interpreted in terms of a reduced coupling between the .beta.-receptor and the metabolic response in isolated brown adipocytes from cold-acclimated animals, which is a result of chronic catecholamine stimulation in vivo.