Adrenocorticotropic hormone stimulates a transient calcium uptake in rat lymphocytes

Freshly isolated rat lymphocytes were tested for corticotropin (ACTH)- dependent calcium uptake. Physiological levels of corticotropin (0.01-1 nM) were found to stimulate both an uptake of ⁴⁵Ca²⁺ and a rise in cAMP. The calcium uptake was delayed by 2 min after ACTH addition, but was rapid and transient after the onset of uptake. The extent of calcium uptake was dose dependent on the corticotropin concentration and reached a maximum by 1 nM. Several fragments of corticotropin were tested for activity; both full- length 1-39 and a functional truncated form, 1-25, had equivalent effects on ⁴⁵Ca influx at 1 nM; however, αMSH-(1-13), ACTH-(11-24), or a mixture of αMSH and ACTH-(11-24) had no effect on ⁴⁵Ca influx. Extracellular calcium uptake was blocked by the calcium channel blockers lanthanum, diltiazem, nifedipine, and ω-conotoxin. Splenic lymphocytes that express ACTH receptors had ligand-dependent calcium uptake, but thymocytes that lack ACTH receptors had no ligand-dependent calcium uptake. A mouse adrenal cell line, Y-1, showed the same ⁴⁵Ca uptake kinetics. These findings demonstrate that both lymphocytes and adrenal cells have a functional ACTH-dependent calcium uptake mechanism.