Direct and Synergistic Interactions of 3,5,3′-Triiodothyronine and the Adrenergic System in Stimulating Sugar Transport by Rat Thymocytes

Joseph Segal; Sidney H. Ingbar

doi:10.1172/JCI109782

Isolated rat thymocytes were preincubated with various catecholamines, alone and together with 3,5,3′-triiodothyronine (T₃), and the accumulation of the glucose analogues, 2-deoxy-d-glucose (2-DG) and 3-O-methylglucose (3-O-MG), was then measured. Epinephrine induced a time- and dose-dependent increase in the 15-min accumulation of 2-DG; at a concentration of 100 μM epinephrine, the effect was evident after a preincubation period of only 5 min. The lowest concentration of epinephrine at which a significant effect was evident was 1 μM. Epinephrine also produced a dose-dependent increase in the accumulation of 3-O-MG, and the lowest concentration at which a significant effect was evident was again 1 μM. Isoproterenol, a β-adrenergic agonist, like epinephrine, increased the accumulation of 2-DG, whereas the α-agonist, phenylephrine, had no effect. The response to epinephrine was inhibited by the β-antagonist, alprenolol, but the α-antagonist, phentolamine, had no effect. As previously demonstrated, T₃ increased 2-DG accumulation, and like epinephrine, its effect was blocked by alprenolol. Neither T₃ (0.1 nM) nor epinephrine (0.1 μM) had any effect when acting alone, but when added together at these concentrations, they significantly increased the accumulation of both 2-DG and 3-O-MG. Neither T₃ with isoproterenol nor T₃ with phenylephrine produced a comparable synergistic effect. But T₃ (0.1 nM) acting with isoproterenol (0.1 μM) and phenylephrine (0.1 μM) together, synergistically increased 2-DG accumulation. In addition, the α-antagonist, phentolamine, which alone had no effect, inhibited the synergistic effect induced by T₃ and epinephrine. The effects of epinephrine and T₃ alone, as well as their combined synergistic effect on 2-DG accumulation, were not blocked by the inhibitor of protein synthesis, puromycin.

From these results we conclude the following: (a) the stimulatory effect of the catecholamines on the accumulation of 2-DG and 3-O-MG reflects an action at the β-receptor; (b) the synergistic interaction between T₃ and epinephrine requires the participation of both β- and α-adrenergic components; (c) T₃ and epinephrine act on 2-DG and 3-O-MG accumulation through a common mechanism or inter-related mechanisms, probably mediated at the β-adrenergic site; and (d) these effects of T₃ and epinephrine, alone and together, are independent of new protein synthesis. These results suggest that, with respect to the response we are describing, T₃ and epinephrine do not act on nuclear mechanisms, but may act instead at the level of the plasma membrane.