Three dihydropyridine (DHP) Ca2+ antagonists were compared with several other organic Ca2+ antagonists with respect to their ability to inhibit depolarization-dependent hormone secretion from the GH4C1 pituitary cell line and from normal rat pituitary cells. The three DHP, nimodipine, nisoldipine, and nifedipine, potently and specifically inhibited KCl-stimulated prolactin secretion from GH4C1 cells (estimated IC50 values: 1.8, 1.8, and 6.0 nM, respectively). Both basal and thyrotropin-releasing hormone-stimulated secretion from GH4C1 cells were much less sensitive to inhibition by the DHP. The inhibition by the DHP was reversible, and their potency was independent of depolarizing concentrations of KCl between 18.8 and 53.8 mM. Other organic antagonists, including verapamil, cinnarizine, and diltiazem, blocked secretion from GH4C1 cells but at much higher concentrations. The estimated IC50 values for these three were 1,000, 1,100, and 3,500 nM, respectively. Depolarization-stimulated prolactin secretion from normal pituitaries was inhibited by the DHP and verapamil at the same concentrations found effective in GH4C1 cells. KCl-stimulated 45Ca2+ uptake by GH4C1 cells was also blocked by DHP at concentrations that inhibited secretion. Since depolarization-stimulated secretion and 45Ca2+ uptake are probably triggered by Ca2+ entering through voltage-sensitive channels, the above results suggest that DHP antagonists potently block these channels in both normal and transformed pituitary cells. These Ca2+ channels appear to be identical in this respect. These findings further suggest a similarity between the Ca2+ channels of endocrine cells and those of smooth muscle and other excitable cells.
Rapid inhibition by somatostatin of vasoactive intestinal peptide-induced prolactin secretion by rat pituitary cells
