scholarly journals Dynorphin and GABAA Receptor Signaling Contribute to Progesterone’s Inhibition of the LH Surge in Female Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (5) ◽  
Author(s):  
Yali Liu ◽  
Xiaofeng Li ◽  
Xi Shen ◽  
Deyana Ivanova ◽  
Geffen Lass ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Gaba Release ◽  
Estradiol Benzoate ◽  
Receptor Signaling ◽  
Gamma Aminobutyric Acid ◽  
Lh Surge ◽  
Female Mice ◽  
Gabaa Receptor Antagonist

Abstract Progesterone can block estrogen-induced luteinising hormone (LH) surge secretion and can be used clinically to prevent premature LH surges. The blocking effect of progesterone on the LH surge is mediated through its receptor in the anteroventral periventricular nucleus (AVPV) of the hypothalamus. However, the underlying mechanisms are unclear. The preovulatory LH surge induced by estrogen is preceded by a significant reduction in hypothalamic dynorphin and gamma-aminobutyric acid (GABA) release. To test the detailed roles of dynorphin and GABA in an LH surge blockade by progesterone, ovariectomized and 17β-estradiol capsule-implanted (OVX/E2) mice received simultaneous injections of estradiol benzoate (EB) and progesterone (P) or vehicle for 2 consecutive days. The LH level was monitored from 2:30 pm to 8:30 pm at 30-minute intervals. Progesterone coadministration resulted in the LH surge blockade. A continuous microinfusion of the dynorphin receptor antagonist nor-BNI or GABAA receptor antagonist bicuculline into the AVPV from 3:00 pm to 7:00 pm reversed the progesterone-mediated blockade of the LH surge in 7 of 9 and 6 of 10 mice, respectively. In addition, these LH surges started much earlier than the surge induced by estrogen alone. However, 5 of 7 progesterone-treated mice did not show LH surge secretion after microinfusion with the GABAB receptor antagonist CGP-35348. Additionally, peripheral administration of kisspeptin-54 promotes LH surge-like release in progesterone treated mice. These results demonstrated that the progesterone-mediated suppression of the LH surge is mediated by an increase in dynorphin and GABAA receptor signaling acting though kisspeptin neurons in the AVPV of the hypothalamus in female mice.

GABA stimulation of gonadotropin-II release in goldfish: involvement of GABAA receptors, dopamine, and sex steroids

1993 ◽  
Vol 265 (2) ◽  
pp. R348-R355 ◽  
Author(s):  
V. L. Trudeau ◽  
B. D. Sloley ◽  
R. E. Peter
Keyword(s):  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Receptor Agonist ◽  
Gabab Receptor ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Turnover Rates ◽  
Pharmacological Agents ◽  
Gabaa Receptor Antagonist ◽  
Gonadotropin Ii

The involvement of gamma-aminobutyric acid (GABA) in regulation of pituitary gonadotropin-II (GTH-II) release was studied in the goldfish. Intraperitoneal injection of GABA (300 micrograms/g) stimulated an increase in serum GTH-II levels at 30 min postinjection. The GABAA receptor agonist muscimol (0.1-10 micrograms/g) stimulated GTH-II in a dose-dependent manner. Baclofen, a GABAB receptor agonist, had a small but significant stimulatory effect at 1 and 10 micrograms/g; the amount of GTH-II released in response to baclofen was significantly less (P < 0.05) than that released by muscimol. Pretreatment of goldfish with bicuculline, a GABAA receptor antagonist, but not saclofen, a GABAB receptor antagonist, blocked the stimulatory effect of GABA on serum GTH-II. Elevation of brain and pituitary GABA levels with the GABA transaminase inhibitor, gamma-vinyl-GABA (GVG), decreased hypothalamic and pituitary dopamine (DA) turnover rates, indicating that GABA may stimulate GTH-II release in the goldfish by decreasing dopaminergic inhibition of GTH-II release. The release of GTH-II stimulated by muscimol and GVG was potentiated by pharmacological agents that decrease inhibitory dopaminergic tone, indicating that DA may also inhibit GABA-stimulated GTH-II release. Based on the linear 24-h accumulation of GABA in brain and pituitary after GVG injection, implantation of testosterone, estradiol, or progesterone, previously shown to regulate the serum GTH-II release response to gonadotropin-releasing hormone and GABA, was also found to modulate GABA synthesis in the brain and pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells

1996 ◽  
Vol 76 (4) ◽  
pp. 2181-2191 ◽  
Author(s):  
R. Lipowsky ◽  
T. Gillessen ◽  
C. Alzheimer
Keyword(s):  
Receptor Antagonist ◽  
Gabab Receptor ◽  
Local Density ◽  
Pyramidal Cells ◽  
Apical Dendrite ◽  
Stratum Radiatum ◽  
Gamma Aminobutyric Acid ◽  
Na Channels ◽  
Voltage Range ◽  
Gabaa Receptor Antagonist

1. Whole cell recordings were performed on the somata of CA1 pyramidal neurons in the rat hippocampal slice preparation Remote synaptic events were evoked by electrical stimulation of Schaffer collateral/commissural fibers in outer stratum radiatum. To isolate non-N-methyl-D-aspartate (NMDA)-mediated excitatory postsynaptic potentials (EPSPs), bath solutions contained the NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acid (D-APV; 30 microM), the gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline (10 microM), and the GABAB receptor antagonists, CGP 35348 (30 microM) or, in some experiments, saclofen (100 microM). 2. Local application of tetrodotoxin (TTX; 0.5-10 microM) into the proximal region of the apical dendrite reduced the peak amplitude of somatically recorded EPSPs by 28% on average. In contrast to dendritic TTX application, injection of TTX into the axosomatic region of the recorded neuron reduced EPSP amplitude by only 12% on average. 3. Spill-over of dendritically applied TTX into stratum pyramidale or into outer stratum radiatum was ruled out experimentally: somatic action potentials and field EPSPs recorded near the stimulation site in outer stratum radiatum remained unaffected by local TTX application. 4. Variations of somatic membrane potential revealed a strong voltage dependence of EPSP reduction after dendritic TTX application with the effect increasing substantially with membrane depolarization. Together with the field recordings from stratum radiatum, this finding argues strongly against a predominantly presynaptic site of TTX action. 5. We therefore ascribe the EPSP decrease after local TTX application to the proximal dendrite to suppression of dendritic Na+ channels, which we assume to give rise to a noninactivating (persistent) Na+ current (INaP) in the subthreshold voltage range. Our data suggest that presumed dendritic INaP produces considerable elevation of remote excitatory signals, thereby compensating for much of their electrotonic attenuation. 6. The experimental findings were related to computer simulations performed on a reduced compartmental model of the CA1 neuron. Because the experimental evidence available so far yields only indirect clues on the strength and distribution of INaP, we allowed considerable variations in these parameters. We also varied both size and location of synaptic input. 7. The major conclusions drawn from these simulations are the following: somatic INaP alone produces little EPSP enhancement; INaP density at the axon hillock/initial segment has to be at least twice the density at the soma to produce substantial EPSP amplification; depending on the density and distribution of dendritic INaP, < or = 80% of a remote synaptic potential arrives at the soma (compared with only 52% in a passive dendrite); synaptic potentials receive progressively more elevation by dendritic INaP the stronger they are; even if restricted to the proximal segment of the apical dendrite, INaP also affects dendritic processing at more distal segments; and spatial distribution rather than local density appears to be the most important parameter determining the role of dendritic INaP in synaptic integration.

Enteric GABA: mode of action and role in the regulation of the peristaltic reflex

1992 ◽  
Vol 262 (4) ◽  
pp. G690-G694 ◽  
Author(s):  
J. R. Grider ◽  
G. M. Makhlouf
Keyword(s):  
Receptor Antagonist ◽  
Motor Neurons ◽  
Gabaa Receptors ◽  
Mode Of Action ◽  
Gabab Receptor ◽  
Circular Muscle ◽  
Gamma Aminobutyric Acid ◽  
Peristaltic Reflex ◽  
Gaba Neurons ◽  
Gabaa Receptor Antagonist

The mode of action of gamma-aminobutyric acid (GABA) and the role of myenteric GABA neurons in the regulation of peristalsis were examined in various preparations of rat colonic muscle. GABA had no contractile, relaxant, or modulatory effect on smooth muscle cells isolated from the circular muscle layer. In innervated circular muscle strips, GABA elicited concentration-dependent relaxation accompanied by release of vasoactive intestinal peptide (VIP). Relaxation and VIP release were inhibited by tetrodotoxin and by the GABAA receptor antagonist bicuculline but not by the GABAB receptor antagonist phaclofen. Relaxation was inhibited by the VIP receptor antagonist VIP-(10-28) implying that VIP release was coupled to muscle relaxation. Relaxation was augmented by atropine implying that GABA also activated cholinergic neurons causing release of acetylcholine that attenuated the relaxant response. This pharmacological profile was evident when GABA was released from intrinsic GABA neurons during peristalsis induced by radial stretch. Blockade of GABAA receptors with bicuculline inhibited the descending relaxation mediated by VIP motor neurons and the ascending contraction mediated by cholinergic motor neurons. Stimulation of these receptors with exogenous GABA had the opposite effect. We conclude that on release from myenteric neurons, GABA acts via GABAA receptors on cholinergic and VIP motor neurons responsible for the two components of the peristaltic reflex.

Hyperpolarizing and depolarizing GABAA receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus

1991 ◽  
Vol 66 (5) ◽  
pp. 1538-1548 ◽  
Author(s):  
N. A. Lambert ◽  
A. M. Borroni ◽  
L. M. Grover ◽  
T. J. Teyler
Keyword(s):  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Gabab Receptor ◽  
Current Source ◽  
Reversal Potential ◽  
Field Potentials ◽  
Postsynaptic Potentials ◽  
One Dimensional ◽  
Area Ca1 ◽  
Gabaa Receptor Antagonist

1. gamma-Aminobutyric acidA (GABAA) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABAA and late, GABAB receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABAA receptor antagonist bicuculline methiodide (BMI; 30 microM) and were not changed by the GABAB receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35,348; 0.1-1.0 mM). CGP 35,348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABAA receptor-mediated population IPSPs (GABAA, fast pIPSPs) and that late field potentials are GABAB receptor-mediated population IPSPs (GABAB, late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration [( Cl-]o) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35,348 (0.4–0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABAA current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4-aminopyridine (50–100 microM), DNQX and APV long-lasting depolarizing GABAA receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)

Oscillatory synaptic interactions between ventroposterior and reticular neurons in mouse thalamus in vitro

1994 ◽  
Vol 72 (4) ◽  
pp. 1993-2003 ◽  
Author(s):  
R. A. Warren ◽  
A. Agmon ◽  
E. G. Jones
Keyword(s):  
Receptor Antagonist ◽  
Gabab Receptor ◽  
Initial Response ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Excitatory Postsynaptic Potential ◽  
Postsynaptic Potential ◽  
Synaptic Interactions ◽  
Gabaa Receptor Antagonist

1. The thalamic reticular nucleus (RTN) has reciprocal connections with relay neurons in the dorsal thalamus. We used whole cell recording in a mouse in vitro slice preparation maintained at room temperature to study the synaptic interactions between the RTN and the ventroposterior thalamic nucleus (VP) during evoked low-frequency oscillations. 2. After a single electrical stimulus of the internal capsule, postsynaptic potentials (PSPs) were recorded in all VP and RTN neurons. In 76% of slices, there was an initial response followed by recurrent PSPs lasting for up to 8 s and with a frequency of approximately 2 Hz in both the VP and RTN. 3. In RTN neurons the initial response consisted of a fast excitatory postsynaptic potential (EPSP) that generated a burst of action potentials. Recurrent PSPs consisted of barrages of EPSPs that often reached burst threshold. The structure of subthreshold EPSP barrages in RTN neurons suggested that they were generated by bursting VP neurons. 4. In VP neurons the stimulus usually evoked a small EPSP followed by a large inhibitory postsynaptic potential (IPSP) that was often followed by a rebound burst. This initial response was often followed by a series of recurrent IPSPs presumably generated by RTN bursts, because intrinsic inhibitory neurons are absent in rodent VP. 5. IPSPs in VP neurons and recurrent EPSPs in RTN neurons were completely abolished by application of a gamma-aminobutyric acid-A (GABAA) receptor antagonist. A GABAB receptor antagonist produced no or little change in either the initial or recurrent response. 6. Recurrent IPSPs in VP neurons were abolished by glutamate receptor antagonists before the initial IPSP, which always remained stimulus dependent. 7. The dependency of recurring IPSPs in VP and recurring EPSPs in RTN upon GABA-mediated inhibition and excitatory amino acid-mediated excitation, plus the character of recurring EPSPs in the RTN strongly suggest that the recurring events were generated through reverse-reciprocal synaptic interactions between VP and RTN neurons. These synaptic interactions most likely play an important role in thalamic oscillations in behavior.

The role of brain acetylcholine in GABAA receptor antagonist-induced blood-pressure changes in rat

1996 ◽  
Vol 317 (2-3) ◽  
pp. 301-307 ◽  
Author(s):  
Tahir Tellioǧlu ◽  
Serap Akin ◽  
Uǧur Özkutlu ◽  
Şule Oktay ◽  
Filiz Onat
Keyword(s):  
Blood Pressure ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Gabaa Receptor Antagonist ◽  
Pressure Changes ◽  
Brain Acetylcholine

scholarly journals Proteomic and Systems Biology Analysis of Monocytes Exposed to Securinine, a GABAA Receptor Antagonist and Immune Adjuvant

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e41278 ◽  
Author(s):  
Matt Shipman ◽  
Kirk Lubick ◽  
David Fouchard ◽  
Rajani Guram ◽  
Paul Grieco ◽  
...  
Keyword(s):  
Systems Biology ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Gabaa Receptor Antagonist ◽  
Immune Adjuvant

Antagonism of the Antinocifensive Action of Halothane by Intrathecal Administration of GABA-A Receptor Antagonists

1996 ◽  
Vol 84 (5) ◽  
pp. 1205-1214 ◽  
Author(s):  
Peggy Mason ◽  
Casey A. Owens ◽  
Donna L. Hammond
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Glycine Receptor ◽  
Intrathecal Administration ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Receptor Antagonists ◽  
Response Latencies ◽  
Halothane Concentration

Background The hind brain and the spinal cord, regions that contain high concentrations of gamma-aminobutyric acid (GABA) and GABA receptors, have been implicated as sites of action of inhalational anesthetics. Previous studies have established that general anesthetics potentiate the effects of gamma-aminobutyric acid at the GABAA receptor. It was therefore hypothesized that the suppression of nocifensive movements during anesthesia is due to an enhancement of GABAA receptor-mediated transmission within the spinal cord. Methods Rats in which an intrathecal catheter had been implanted 1 week earlier were anesthetized with halothane. Core temperature was maintained at a steady level. After MAC determination, the concentration of halothane was adjusted to that at which the rats last moved in response to tail clamping. Saline, a GABAA, a GABAB, or glycine receptor antagonist was then injected intrathecally. The latency to move in response to application of the tail clamp was redetermined 5 min later, after which the halothane concentration was increased by 0.2%. Response latencies to application of the noxious stimulus were measured at 7-min intervals during the subsequent 35 min. To determine whether these antagonists altered baseline response latencies by themselves, another experiment was conducted in which the concentration of halothane was not increased after intrathecal administration of GABAA receptor antagonists. Results Intrathecal administration of the GABAA receptor antagonists bicuculline (0.3 micrograms) or picrotoxin (0.3, 1.0 micrograms) antagonized the suppression of nocifensive movement produced by the small increase in halothane concentration. In contrast, the antinocifensive effect of the increase in halothane concentration was not attenuated by the GABAB receptor antagonist CGP 35348 or the glycine receptor antagonist strychnine. By themselves, the GABAA receptor antagonists did not alter response latency in rats anesthetized with sub-MAC concentrations of halothane. Conclusions Intrathecal administration of bicuculline or picrotoxin, at doses that do not change the latency to pinch-evoked movement when administered alone, antagonized the suppression of noxious-evoked movement produced by halothane concentrations equal to or greater than MAC. These results suggest that enhancement of GABAA receptor-mediated transmission within the spinal cord contributes to halothane's ability to suppress nocifensive movements.

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