KN-62, A CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE-II INHIBITOR, INHIBITS HIGH POTASSIUM-STIMULATED PROLACTIN SECRETION AND INTRACELLULARCALCIUM INCREASES IN ANTERIOR-PITUITARY-CELLS

In isolated rat anterior pituitary cells, KN-62 (10 mu M), an isoquino line sulfonamide inhibitor of calcium/calmodulin-dependent protein kin ase II, inhibited high KCl(50 mM)-stimulated prolactin secretion almos t completely, with an IC50 of 95 nM. KN-62 inhibited TRH-induced prola ctin secretion less effectively. KN-04, a compound that is over 100-fo ld less active in inhibiting purified calcium/calmodulin-dependent pro tein kinase II: also inhibited high KCl-stimulated prolactin secretion with an IC50 of 500 nM. KN-62 and KN-04 (10 mu M) both inhibited high KCl-stimulated increases in intracellular Ca2+ concentrations. We con clude that KN-62 and KN-04 inhibit activation of voltage-dependent cal cium channels in anterior pituitary cells either directly or indirectl y.