Participation of voltage-dependent calcium channels in the action of gonadotropin-releasing hormone

• Published in: The Journal of biological chemistry 1986-07, Vol.261 (20), p.9105-9108
• Main Authors: Chang, J P, McCoy, E E, Graeter, J, Tasaka, K, Catt, K J
• Format: Article
• Language: English
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Aminoquinolines; Animals; Biological and medical sciences; Calcimycin - pharmacology; Calcium - metabolism; Cell physiology; Cells, Cultured; Cytoplasm - metabolism; Ethers - pharmacology; Female; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; Gonadotropin-Releasing Hormone - pharmacology; Hormonal regulation; Ion Channels - physiology; Ionomycin; Luteinizing Hormone - metabolism; Molecular and cellular biology; Nifedipine - analogs & derivatives; Nifedipine - pharmacology; Nitrendipine; Pituitary Gland, Anterior - drug effects; Pituitary Gland, Anterior - metabolism; Potassium - pharmacology; Rats; Rats, Inbred Strains
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)67623-9

The roles of calcium ions and voltage-sensitive calcium channels in gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release were investigated in rat anterior pituitary cells. The calcium ionophores A23187 and ionomycin stimulated LH release from cultured pituitary cells, in which ionomycin (5 X 10(-5) M) was as effective as a maximal concentration of GnRH (10(-8) M). In addition, a concentration of the calcium channel agonist methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine- 5-carboxylate (BK 8644) (10(-8) M), which did not alter basal LH release, potentiated the ability of submaximal (10(-10) and 10(-9) M) doses of GnRH to increase LH secretion. Furthermore, concentrations of the calcium channel antagonist nitrendipine (10(-8)-10(-5) M) that did not alter basal LH release, inhibited GnRH-stimulated LH secretion by 30-40%. Nitrendipine (10(-8) M) also blocked the potentiation of GnRH-induced LH secretion by BK 8644. During column perifusion of pituitary cells, 10(-8) M nitrendipine reduced the LH response to a 2-min pulse of 10(-8) M GnRH by about 40%. In Quin-2-loaded pituitary cells, supramaximal doses (10(-6) M) of a potent GnRH agonist rapidly elevated cytoplasmic Ca2+ by 50-100 nM. Concomitant treatment with nitrendipine decreased the GnRH agonist-induced Ca2+ signal by 40-60%. These results indicate that increases in intracellular Ca2+ via voltage-sensitive calcium channels partially reproduce GnRH action, and also that GnRH causes activation of such channels. However, the increase in cytoplasmic Ca2+ concentration during GnRH action must originate in part from mobilization of internal Ca2+ stores, and its relatively small magnitude may be consistent with the concomitant activation of protein kinase C as an intermediate step in GnRH action.