Multiple classes of calcium channels in mouse pituitary tumor cells

Synthetic corticotropin-releasing factor (CRF) is a potent adrenocorticotropin (ACTH) secretagogue in the mouse pituitary tumor cell strain AtT20/D16v (D16). In the absence of added calcium in the incubation medium a dose of 5 nM CRF stimulates ACTH secretion 2-fold over control values while at medium calcium concentrations greater than 1 mM the same dose of CRF elicits a 3-fold stimulation. In the presence of EGTA or of the calcium antagonists verapamil, cobalt, or lanthanum the CRF effect is abolished. Depolarizing concentrations of extracellular K+ lead to a rapid increase in cell-associated calcium, a response which is inhibited by the dihydropyridine calcium antagonist nimodipine. Although treatment with CRF does not alter the concentration of cell-associated calcium in D16 cells, ACTH secretion stimulated by both CRF and elevated medium K+ are inhibited by nimodipine in a dose-related manner. The results indicate that D16 cells possess both voltage-sensitive and CRF-activated calcium channels.