Abstract
In previous studies we have shown that the thyroid hormone T3 induces a prompt increase in the cAMP concentration of rat thymocytes in vitro. This is followed by and very likely leads to an increase in cellular uptake of the glucose analog 2-deoxyglucose (2-DG). Since these effects of T3 were shown to require the presence of Ca2+ in the suspending medium, it seemed reasonable to determine whether T3 would influence the metabolism of calcium itself. In standard medium containing 1 mM Ca2+ and 45Ca as a tracer, T3 induced a very prompt, dose-related, but transient, increase in thymocyte calcium accumulation. This effect was evident within the first minute after the addition of T3 (including processing time) and is to our knowledge the most rapid effect of T3 yet demonstrated. The effect reached a maximum very shortly thereafter and then abated within a few minutes. Uptake of 45Ca from Ca2+-free medium (5 microM Ca2+ as a contaminant) was also increased by T3, but under these conditions, the increase was sustained for the entire 120-min period of study. At a concentration of 25 microM, lanthanum (La3+) unexpectedly produced a rapid and marked (4- to 6-fold) increase in 45Ca accumulation in the thymocytes. The increase in cellular calcium accumulation produced by La3+ was not associated with any effect on thymocyte cAMP concentration or 2-deoxyglucose (2-DG) uptake. However, La3+ potentiated the response of the cell to T3 in respect to calcium accumulation, cAMP concentration, and 2-DG uptake, shifting the dose-response curve of the latter two effects to the left. In view of the calcium dependence of the T3 effect on thymocyte cAMP concentration and 2-DG uptake, and the effect of La3+ to concomitantly enhance the sensitivity of the cell to the effects of T3 on calcium accumulation and cAMP and 2-DG metabolism, we suggest that the prompt increase in cellular Ca2+ uptake induced by T3 that we demonstrated is causally related to its subsequent effect on cellular cAMP concentration and 2-DG uptake.
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