Ca 2+ channel agonists enhance thyrotropin-releasing hormone-induced inositol phosphates and prolactin secretion

Abstract

The dihydropyridine Ca 2+ channel activator BAY K 8644 (1 μM) stimulated basal prolactin secretion from perifused primary cultures of anterior pituitary cells and potentiated the stimulation of prolactin secretion by 1 μM thyrotropin-releasing hormone (TRH) 5-fold over 30 min. This potentiation was mimicked by other dihydropyridine agonists CGP 28392 and (+)-SDZ 202–791 and by (−)-BAY K. 8644 (1 μM), but not by (+)-BAY K 8644. The Ca 2+ channel antagonist nimodipine, at a concentration sufficient to block BAY K 8644-stimulated 45Ca 2+ uptake in GH 4C 1 anterior pituitary tumor cells, decreased basal prolactin secretion and blocked the enhancement of basal and TRH-stimulated secretion by BAY K 8644. These results suggest that dihydropyridine agonists potentiate TRH-induced secretion through interaction with known stereospecific sites on Ca 2+ channels. In gh 4c 1 cells, BAY K 8644 alone did not affect inositol polyphosphate accumulation, but potentiated TRH-stimulated accumulation of inositol 1,3,4-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. Accumulation of the Ca 2+ -mobilizing isomer inositol 1,4,5-trisphosphate was not potentiated, suggesting that potentiation of TRH-stimulated hormone secretion by BAY K 8644 does not result from synergistic stimulation of phospholipase C, but may correlate with enhanced inositol trisphosphate-3-kinase activity.