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

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Abstract

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.

Authors

Joseph Segal, Sidney H. Ingbar