Gonadotropin releasing hormone modulates gamma-aminobutyric acid-evoked intracellular calcium increase in immortalized hypothalamic gonadotropin releasing hormone neurons.
To examine the functional role of calcium signaling in the interactive modulation of gonadotropin releasing hormone (GnRH) neurons by gamma-aminobutyric acid (GABA) and GnRH itself, we analyzed the intracellular calcium level ([Ca2+]i), using fura-2AM fluorescent dye in immortalized hypothalamic GT1-1 cells. GT1-1 cells showed spontaneous [Ca2+]i oscillations, which were dependent on extracellular Ca2+ level, L-type Ca2+ channel and SK-type K+ channel. When GABA or a specific GABAA type receptor agonist, muscimol was applied to the media, [Ca2+]i rapidly increased through L-type Ca2+ channel in a dose-dependent manner, and subsequently decreased below the basal level without any oscillation. However, a specific GABAB type receptor agonist, baclofen showed no effect. On the other hand, application of GnRH or its potent agonist buserelin, rapidly abolished the spontaneous [Ca2+]i oscillations. Interestingly, a prior treatment with buserelin abolished GABA-evoked increase in [Ca2+]i in a noncompetitive manner. Since buserelin also blocked K(+)-evoked increase in [Ca2+]i, we suggest that GnRH may block spontaneous [Ca2+]i oscillation through modulating the L-type [Ca2+]i channel activity. These results show that GABAergic agents may exert both stimulatory and inhibitory controls over the GnRH neuronal activity, and GnRH can block the stimulatory effect of GABA, implicating the possible existence of an ultrashort feedback circuit.
Sun
W
W
Department of Molecular Biology, College of Natural Sciences, Seoul National University, South Korea.
Jarry
H
H
Wuttke
W
W
Kim
K
K
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002064:Buserelin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D016257:Fura-2; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology* / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007202:Indicators and Reagents; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D015220:Calcium Channels; D018755:GABA Agonists; D018757:GABA Modulators; D007202:Indicators and Reagents; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D007987:Gonadotropin-Releasing Hormone; D005680:gamma-Aminobutyric Acid; D002064:Buserelin; D002118:Calcium; D016257:Fura-2