Participation of voltage-dependent calcium channels in the action of gonadotropin-releasing hormone.
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.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000634:Aminoquinolines; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004987:Ethers / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007473:Ion Channels / Q000502:physiology*; D015759:Ionomycin; D007986:Luteinizing Hormone / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000634:Aminoquinolines; D004987:Ethers; D005456:Fluorescent Dyes; D007473:Ion Channels; D007987:Gonadotropin-Releasing Hormone; D000001:Calcimycin; D015759:Ionomycin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007986:Luteinizing Hormone; D009568:Nitrendipine; D009543:Nifedipine; C035739:Quin2; D011188:Potassium; D002118:Calcium