Nitrendipine and Ω-conotoxin modulate gonadotropin release and gonadotrope [Ca2+]i

Michael Blotner, Gary A. Shangold*, Everett Y. Lee, Shawn N. Murphy, Richard J. Miller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

We have examined the pharmacology of the voltage-sensitive Ca2+ channels (VSCCs) that mediate gonadotropin secretion from primary cultures of rat pituitary cells, stimulated by either cell depolarization or by binding of gonadotropin-releasing hormone (GnRH). We also measured single-cell [Ca2+]i transients using fura-2 in gonadotropes identified by a reverse hemolytic plaque assay employing an antiserum to luteinizing hormone (LH). Cell depolarization evoked by either 50 mM K+ or 30 μM veratridine induced 2- to 6-fold increases in gonadotropin secretion over basal levels. GnRH caused 6- to 20-fold increases in follicle-stimulating hormone (FSH) and LH secretion, respectively, with maximal stimulation at 100 nM GnRH. K+- or GnRH-induced FSH release was largely prevented by co-incubation with 1 mM CdCl. Tetrodotoxin (TTX, 5 μM) prevented the veratridine-, but not the K+- or GnRH-induced, stimulation of FSH secretion. Nitrendipine (Ntd, 1 μM) produced 35-50% inhibition (NS) of both FSH and LH release stimulated by either 50 mM K+ or 100 nM GnRH. Ntd also inhibited the K+-induced [Ca2+] i rise (>90%), as well as the secondary, plateau phase of the GnRH-induced elevation of [Ca2+]i (100% inhibition). Omega-conotoxin (Ω-CgTx, 100 nM) partially suppressed FSH and LH release (NS) due to both K+ (33% each) and GnRH (44% and 18%, respectively). Ω-CgTx showed variable effects on [Ca2+]i transients evoked by K+ or GnRH ranging from clear inhibition to no effect. We conclude that influx of extracellular Ca2+ is one of several fundamental events underlying the depolarization- or receptor-activated release of LH and FSH, and that this influx can be inhibited by dihydropyridine-sensitive ('L') Ca2+ channels. Two classes of L-channels may exist in gonadotropes, that differ in their sensitivity to Ω-CgTx.

Original languageEnglish (US)
Pages (from-to)205-216
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume71
Issue number3
DOIs
StatePublished - Jul 9 1990

Keywords

  • Calcium channel blocker
  • Calcium, intracellular
  • Cell culture
  • Gonadotropin
  • Microfluorimetry
  • Voltage-sensitive calcium channel

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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