The ability of calcium to change cyclic AMP from a stimulator to an inhibitor of thymic lymphoblast proliferation

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Abstract
Calcium is a major regulator of thymic lymphoblast proliferation in vivo and in vitro. The proliferative activity of the lymphoblasts in thymic lymphocyte (thymocyte) populations in vitro is both constant and low in the presence of calcium concentrations between 0 and 1.0 mM, but higher concentrations increase proliferation by an endogenous cyclic AMP‐mediated promotion of the initiation of DNA synthesis.Lower concentrations (10−7 to 10−5 M) of exogenous cyclic AMP (but not 5′‐AMP) stimulate lymphoblast proliferation in a low‐calcium (0.5 mM) medium, but higher concentrations do not. However, all exogenous cyclic AMP concentrations between 10−7 and 10−3 M (but again not 5′‐AMP) block the stimulation of lymphoblast proliferation in a high‐calcium (1.5 mM) medium. Exogenous cyclic AMP does not prevent calcium from “activating” lymphoblasts, but it reversibly blocks the reaction responsible for the initiation of DNA synthesis in these stimulated cells. Finally, cyclic AMP's inhibitory action, in contrast to its stimulatory action in low‐calcium medium, is not specific for the cyclic nucleotide since a low, non‐mitogenic concentration of cyclic GMP also prevents calcium from stimulating DNA synthesis and cell proliferation.
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