Nitrendipine and Ω-conotoxin modulate gonadotropin release and gonadotrope [Ca2+]i
| Autor: | Richard J. Miller, Everett Y. Lee, Shawn N. Murphy, Michael Blotner, Gary A. Shangold |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
endocrine system
medicine.medical_specialty medicine.drug_class Gonadotropin-releasing hormone Biology Gonadotropic cell Peptides Cyclic Biochemistry Membrane Potentials Gonadotropin-Releasing Hormone chemistry.chemical_compound Follicle-stimulating hormone Endocrinology Pituitary Gland Anterior omega-Conotoxin GVIA Internal medicine medicine Animals Omega-Conotoxin GVIA Molecular Biology Nitrendipine Rats Inbred Strains Luteinizing Hormone Calcium Channel Blockers Rats Gonadotropin secretion chemistry Calcium Female Calcium Channels Follicle Stimulating Hormone Gonadotropin Secretory Rate Veratridine Luteinizing hormone Ion Channel Gating hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular and Cellular Endocrinology. 71:205-216 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/0303-7207(90)90026-5 |
| Popis: | 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 microM 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 microM) prevented the veratridine-, but not the K(+)- or GnRH-induced, stimulation of FSH secretion. Nitrendipine (Ntd, 1 microM) 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 (greater than 90%), as well as the secondary, plateau phase of the GnRH-induced elevation of [Ca2+]i (100% inhibition). Omega-conotoxin (omega-CgTx, 100 nM) partially suppressed FSH and LH release (NS) due to both K+ (33% each) and GnRH (44% and 18%, respectively). omega-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 omega-CgTx. |
| Databáze: | OpenAIRE |
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