Flunarizine, a calcium influx blocker, inhibits TRH- but not potassium-stimulated prolactin secretion

Abstract. The effect of flunarizine on the secretion of prolactin from monolayer cultures of normal rat pituitary cells has been determined. Both basal and TRHstimulated secretion were found to be significantly inhibited by micromolar concentrations of flunarizine, whereas depolarization (high K+)-stimulated secretion was virtually unaffected. These results indicate that TRH-stimulated prolactin secretion probably involves calcium influx and that flunarizine may be useful as a probe for particular Ca2+ channels.

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Dihydropyridine Ca2+ antagonists: potent inhibitors of secretion from normal and transformed pituitary cells

AJP Cell Physiology ◽

10.1152/ajpcell.1985.248.5.c510 ◽

1985 ◽

Vol 248 (5) ◽

pp. C510-C519 ◽

Cited By ~ 46

Author(s):

J. J. Enyeart ◽

T. Aizawa ◽

P. M. Hinkle

Keyword(s):

Endocrine Cells ◽

Hormone Secretion ◽

Prolactin Secretion ◽

Pituitary Cells ◽

Excitable Cells ◽

Rat Pituitary ◽

Ic50 Values ◽

Normal Rat ◽

Rat Pituitary Cells ◽

Ca2 Channels

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.

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Modulation of prolactin secretion by contraceptive progestins in cultured rat pituitary cells in vitro

Acta Endocrinologica ◽

10.1530/acta.0.117s188 ◽

1988 ◽

Vol 117 (4_Suppl) ◽

pp. S188-S189

Author(s):

L. KIESEL ◽

T. RABE ◽

D. SCHOLZ ◽

V. KIRSCHNER ◽

B. RUNNEBAUM

Keyword(s):

Prolactin Secretion ◽

Pituitary Cells ◽

Rat Pituitary ◽

Rat Pituitary Cells

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A COMPARISON OF THE EFFECTS OF FOUR ERGOT DERIVATIVES ON PROLACTIN SECRETION BY DISPERSED RAT PITUITARY CELLS

Journal of Endocrinology ◽

10.1677/joe.0.0870095 ◽

1980 ◽

Vol 87 (1) ◽

pp. 95-103 ◽

Cited By ~ 11

Author(s):

G. DELITALA ◽

T. YEO ◽

ASHLEY GROSSMAN ◽

N. R. HATHWAY ◽

G. M. BESSER

Keyword(s):

Anterior Pituitary ◽

Ergot Alkaloids ◽

Prolactin Secretion ◽

Pituitary Cells ◽

Inhibitory Effects ◽

Prolactin Release ◽

Ergot Derivatives ◽

Rat Pituitary ◽

Rat Pituitary Cells

The inhibitory effects of dopamine and various ergot alkaloids on prolactin secretion were studied using continuously perfused columns of dispersed rat anterior pituitary cells. Bromocriptine (5 nmol/l) and lisuride hydrogen maleate (5 nmol/l) both inhibited prolactin secretion, the effects persisting for more than 3 h after the end of the administration of the drugs. A similar although less long-lasting effect was observed with lergotrile (50 nmol/l) and the new ergoline derivative, pergolide (5 nmol/l). These effects contrasted with the rapid disappearance of the action of dopamine. The potency estimates of the ergots relative to that of dopamine were: lergotrile, 2·3; bromocriptine, 13; lisuride, 15; pergolide, 23. The dopamine-receptor blocking drugs, metoclopramide and haloperidol, antagonized the prolactin release-inhibiting activity of the compounds; bromocriptine and lisuride showed the highest resistance to this dopaminergic blockade. The results suggested that the direct effect of the ergot derivatives on dispersed pituitary cells was mediated through dopamine receptors and emphasized the long-lasting action of bromocriptine and lisuride in vitro.

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