Direct and synergistic interactions of 3,5,3'-triiodothyronine and the adrenergic system in stimulating sugar transport by rat thymocytes.

Isolated rat thymocytes were preincubated with various catecholamines, alone and together with 3,5,3'-triiodothyronine (T(3)), 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 muM 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 muM. 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 muM. Isoproterenol, a beta-adrenergic agonist, like epinephrine, increased the accumulation of 2-DG, whereas the alpha-agonist, phenylephrine, had no effect. The response to epinephrine was inhibited by the beta-antagonist, alprenolol, but the alpha-antagonist, phentolamine, had no effect. As previously demonstrated, T(3) increased 2-DG accumulation, and like epinephrine, its effect was blocked by alprenolol. Neither T(3) (0.1 nM) nor epinephrine (0.1 muM) 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 T(3) with isoproterenol nor T(3) with phenylephrine produced a comparable synergistic effect. But T(3) (0.1 nM) acting with isoproterenol (0.1 muM) and phenylephrine (0.1 muM) together, synergistically increased 2-DG accumulation. In addition, the alpha-antagonist, phentolamine, which alone had no effect, inhibited the synergistic effect induced by T(3) and epinephrine. The effects of epinephrine and T(3) 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 beta-receptor; (b) the synergistic interaction between T(3) and epinephrine requires the participation of both beta- and alpha-adrenergic components; (c) T(3) and epinephrine act on 2-DG and 3-O-MG accumulation through a common mechanism or inter-related mechanisms, probably mediated at the beta-adrenergic site; and (d) these effects of T(3) and epinephrine, alone and together, are independent of new protein synthesis. These results suggest that, with respect to the response we are describing, T(3) and epinephrine do not act on nuclear mechanisms, but may act instead at the level of the plasma membrane.