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GABA inhibition of immortalized gonadotropin-releasing hormone neuronal excitability involves GABA(A) receptors negatively coupled to cyclic adenosine monophosphate formation.
- Source :
-
Endocrine [Endocrine] 2001 Mar; Vol. 14 (2), pp. 189-95. - Publication Year :
- 2001
-
Abstract
- Gamma-aminobutyric acid (GABA) has been implicated in the regulation of reproduction, particularly in the developmental modulation of gonadotropin-releasing hormone (GnRH) secretion. GnRH neurons are innervated by GABA-containing processes, and the administration of GABA stimulates and inhibits GnRH secretion in vivo and in vitro. We have previously shown that GABA can exert both of these actions in sequence, by acting directly on immortalized GnRH neurons. While the stimulation is the result of a GABA(A) receptor-mediated depolarization of the plasma membrane, the mechanism involved in the delayed inhibition is the subject of the present investigation. GABA (1 nM-10 microM) decreased the intracellular concentration of cyclic adenosine monophosphate (cAMP) in a dose- and time-dependent fashion. This effect was blocked by bicuculline and mimicked by muscimol but not by baclofen. To analyze the effect of GABA on cellular excitability, we used fura-2 loaded GT1-7 cells. Activation of voltage-sensitive calcium channels by high K+-induced depolarization (35 mM) increased [Ca2+]i. GABA (10 microM) and muscimol (10 microM) reduced the amplitude of K+-induced [Ca2+]i transients. This inhibition was blocked by forskolin (20 microM) or 8-Br-cAMP (1 mM). Altogether, these results show that GABA(A) receptors mediate a sustained inhibitory effect of GABA on GnRH neurons, and suggest the involvement of the cAMP pathway decreasing cellular excitability.
- Subjects :
- 8-Bromo Cyclic Adenosine Monophosphate pharmacology
Baclofen pharmacology
Bicuculline pharmacology
Calcium metabolism
Calcium Channels drug effects
Calcium Channels physiology
Cell Line, Transformed
Cell Membrane physiology
Colforsin pharmacology
Kinetics
Muscimol pharmacology
Potassium pharmacology
Cyclic AMP metabolism
Gonadotropin-Releasing Hormone metabolism
Neurons drug effects
Neurons physiology
Receptors, GABA-A physiology
gamma-Aminobutyric Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1355-008X
- Volume :
- 14
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Endocrine
- Publication Type :
- Academic Journal
- Accession number :
- 11394636
- Full Text :
- https://doi.org/10.1385/ENDO:14:2:189