Influence of GABAergic mechanisms on baroreceptor inputs to nucleus tractus solitarii of rats

1996 ◽  
Vol 271 (3) ◽  
pp. H931-H936 ◽  
Author(s):  
P. Ruggeri ◽  
C. E. Cogo ◽  
V. Picchio ◽  
C. Molinari ◽  
R. Ermirio ◽  
...  

The firing frequency of baroreceptive neurons in the nucleus tractus solitarii (NTS) during microiontophoretic application of muscimol, a gamma-aminobutyric acid (GABA)A agonist, or baclofen, a GABAB agonist, was monitored in anesthetized rats. Muscimol decreased the spontaneous discharge of 69 of 73 (94.5%) NTS baroreceptive neurons without affecting the remaining four neurons (5.5%). The statistical comparison on a bin-by-bin basis of the peri-R wave interval histograms of the discharge of each NTS neuron showed that the inhibitory action of muscimol was always exerted on the whole neuronal discharge independently of its correlation to the cardiac cycle. Baclofen inhibited 60 of 73 (82.2%) NTS neurons without affecting the remaining 13 neurons (17.8%). In 31 of 60 (51.7%) neurons inhibited by baclofen, this substance significantly affected only pulse-synchronous peaks of neuronal discharge without significant inhibition of the neuronal firing between cardiac cycle-related peaks. Fifty-eight of 73 (79.5%) NTS neurons studied were inhibited by both muscimol and baclofen, 11 neurons (15%) only by muscimol, 2 neurons (2.7%) only by baclofen, and 2 neurons (2.7%) were unaffected by both substances. These results demonstrate that both GABAA and GABAB receptors mediate inhibition of the spontaneous discharge in the great majority of the NTS baroreceptive neurons studied and suggest different functions of the two types of GABA receptors in influencing baroreceptor inputs to the NTS.

1990 ◽  
Vol 63 (1) ◽  
pp. 173-180 ◽  
Author(s):  
A. Miwa ◽  
M. Ui ◽  
N. Kawai

1. We have examined the effects of L-glutamate and gamma-aminobutyric acid (GABA) on the presynaptic membrane of spiny lobster by the use of intra-axonal recording near the nerve terminals. 2. Application of glutamate to the synaptic region produced hyperpolarization in the presynaptic membrane but depolarization in the postsynaptic membrane. The presynaptic glutamate potential (PGP) is generated by an activation of K+ channels, as evidenced by its dependence on external K+ concentration. 3. The PGP was not affected by a spider toxin (JSTX), which blocks the postsynaptic glutamate receptor. By contrast, pertussis toxin (IAP) effectively blocked the PGP without affecting the resting conductance channels or action potentials in the presynaptic membrane. 4. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), a hydrolysis-resistant analogue of GTP, blocked the PGP, suggesting the involvement of a G protein in the generation of K+ current. 5. Application of GABA induced depolarization or hyperpolarization in the presynaptic axon depending on the resting membrane potential. By reducing external Cl-, GABA-induced hyperpolarizations were converted to depolarizations, indicating that they are mainly mediated by Cl-. 6. In contrast to GABA, baclofen consistently induced hyperpolarization in low Cl- solution as well as in normal solution. Baclofen-induced hyperpolarization was blocked by IAP, indicating the mediation of G protein. 7. These results suggest that the presynaptic membrane of lobster neuromuscular synapse has entirely different types of amino-acid receptors from those in the postsynaptic membrane. Both the excitatory and the inhibitory axonal membrane have glutamate ("glutamateB") and GABAB receptors, which activate K+ channels via G protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 530
Author(s):  
Oliviero Bruni ◽  
Luigi Ferini-Strambi ◽  
Elena Giacomoni ◽  
Paolo Pellegrino

Sleep is an essential component of physical and emotional well-being, and lack, or disruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control. Currently available evidence suggests that herbal extracts may exert some of their hypnotic and anxiolytic activity through interacting with GABA receptors and modulating GABAergic signaling in the brain, but their mechanism of action in the treatment of insomnia is not completely understood.


1996 ◽  
Vol 76 (3) ◽  
pp. 2005-2019 ◽  
Author(s):  
W. A. Hare ◽  
W. G. Owen

1. It is widely believed that signals contributing to the receptive field surrounds of retinal bipolar cells pass from horizontal cells to bipolar cells via GABAergic synapses. To test this notion, we applied gamma-aminobutyric acid (GABA) agonists and antagonists to isolated, perfused retinas of the salamander Ambystoma tigrinum while recording intracellularly from bipolar cells, horizontal cells, and photoreceptors. 2. As we previously reported, administration of the GABA analogue D-aminovaleric acid in concert with picrotoxin did not block horizontal cell responses or the center responses of bipolar cells but blocked the surround responses of both on-center and off-center bipolar cells. 3. Surround responses were not blocked by the GABA, antagonists picrotoxin or bicuculline, the GABAB agonist baclofen or the GABAB antagonist phaclofen, and the GABAC antagonists picrotoxin or cis-4-aminocrotonic acid. Combinations of these drugs were similarly ineffective. 4. GABA itself activated a powerful GABA uptake mechanism in horizontal cells for which nipecotic acid is a competitive agonist. It also activated, both in horizontal cells and bipolar cells, large GABAA conductances that shunted light responses but that could be blocked by picrotoxin or bicuculline. 5. GABA, administered together with picrotoxin to block the shunting effect of GABAA activation, did not eliminate bipolar cell surround responses at concentrations sufficient to saturate the known types of GABA receptors. 6. Surround responses were not blocked by glycine or its antagonist strychnine, or by combinations of drugs designed to eliminate GABAergic and glycinergic pathways simultaneously. 7. Although we cannot fully discount the involvement of a novel GABAergic synapse, the simplest explanation of our findings is that the primary pathway mediating the bipolar cell's surround is neither GABAergic nor glycinergic.


1991 ◽  
Vol 65 (3) ◽  
pp. 680-692 ◽  
Author(s):  
R. A. Stockton ◽  
M. M. Slaughter

1. The effects of inhibitory amino acid transmitters on horizontal cells in the superfused amphibian retina were studied by the use of conventional intracellular recording techniques. 2. Gamma-aminobutyric acid (GABA) caused a calcium-independent depolarization of horizontal cells in mud puppy and tiger salamander. This action was mimicked by muscimol but not baclofen (BAC) and blocked by bicuculline and picrotoxin (PTX), matching the GABAa receptor profile. 3. The purported GABA uptake inhibitors nipecotate (NPA) and guvacine (GUV) acted as GABAa agonists, having pharmacological properties very similar to GABA itself. These agents also activated receptors of amacrine and ganglion cells, causing membrane polarizations similar to GABA. Concentrations of these analogues that did not activate the GABAa receptor (submillimolar) did not lower the effective dose of GABA, even after prolonged application. 4. Glycine (GLY) also depolarized horizontal cells, but only in approximately 25% of the horizontal cells was the amplitude of the depolarization as great as GABA. The glycine response was blocked by both strychnine (STR, 10 microM) and PTX (100 microM). In contrast, the action of GABA was unaffected by STR. 5. Ion substitution and channel-blocking agents indicated that the effects of applied GABA and GLY were independent of both external sodium and calcium. 6. The results suggest that GABA receptors on horizontal cells may act 1) as a positive feedback system to modulate the light response and 2) as a mechanism for chemical coupling between horizontal cells.


2014 ◽  
Vol 369 (1654) ◽  
pp. 20130602 ◽  
Author(s):  
Simon Höft ◽  
Stephanie Griemsmann ◽  
Gerald Seifert ◽  
Christian Steinhäuser

Astrocytes may express ionotropic glutamate and gamma-aminobutyric acid (GABA) receptors, which allow them to sense and to respond to neuronal activity. However, so far the properties of astrocytes have been studied only in a few brain regions. Here, we provide the first detailed receptor analysis of astrocytes in the murine ventrobasal thalamus and compare the properties with those in other regions. To improve voltage-clamp control and avoid indirect effects during drug applications, freshly isolated astrocytes were employed. Two sub-populations of astrocytes were found, expressing or lacking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. AMPA receptor-bearing astrocytes displayed a lower Kir current density than cells lacking the receptors. In contrast, all cells expressed GABA A receptors. Single-cell RT-PCR was employed to identify the receptor subunits in thalamic astrocytes. Our findings add to the emerging evidence of functional heterogeneity of astrocytes, the impact of which still remains to be defined.


1989 ◽  
Vol 257 (1) ◽  
pp. R246-R251 ◽  
Author(s):  
M. Lisa ◽  
E. Marmo ◽  
J. H. Wible ◽  
J. A. DiMicco

We have previously shown that the physiological and behavioral manifestations of emotional stress are produced when drugs impairing gamma-aminobutyric acid (GABA)-mediated synaptic inhibition are injected into the posterior hypothalamic nucleus in rats [Wible, J.H., Jr., F.C. Luft, and J.A. DiMicco. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R680-R687, 1988]. The purpose of this study was to assess further the potential role of GABA receptors in this region in the response to stress using muscimol, a GABAA receptor agonist. In six chronically instrumented conscious rats, air stress after vehicle treatment evoked marked and sustained tachycardia (+130 +/- 14 beats/min at +10 min) accompanied by a less dramatic increase in arterial pressure (+14 +/- 3 mmHg). Microinjection of muscimol (10 ng; 88 pmol) at the same posterior hypothalamic site in which GABA blockade causes cardiovascular changes similar to those seen in stress produced a modest depression of cardiovascular function in unstressed animals (-28 +/- 5 beats/min and -6 +/- 3 mmHg). However, similar treatment with muscimol virtually abolished the stress-induced tachycardia in the same rats (+9 +/- 8 beats/min), while having no significant effect on baroreflex-evoked increases in heart rate caused by intravenous infusion of sodium nitroprusside (4 micrograms). These findings support a role for activation of neurons in the posterior nucleus of the hypothalamus in the generation of stress-induced cardiovascular changes and for control of this mechanism by local GABA receptors.


1999 ◽  
Vol 260 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Masahiko Suzuki ◽  
Mitsue Tetsuka ◽  
Makoto Endo

2009 ◽  
Vol 12 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Evgeniya A. Zyablitseva ◽  
Nikolay S. Kositsyn ◽  
Galina I. Shul'gina

The research described here investigates the role played by inhibitory processes in the discriminations made by the nervous system of humans and animals between familiar and unfamiliar and significant and nonsignificant events. This research compared the effects of two inhibitory mediators of gamma-aminobutyric acid (GABA): 1) phenibut, a nonselective agonist of ionotropic GABAAand metabotropic GABABreceptors and 2) gaboxadol a selective agonist of ionotropic GABAAreceptors on the process of developing active defensive and inhibitory conditioned reflexes in alert non-immobilized rabbits. It was found that phenibut, but not gaboxadol, accelerates the development of defensive reflexes at an early stage of conditioning. Both phenibut and gaboxadol facilitate the development of conditioned inhibition, but the effect of gaboxadol occurs at later stages of conditioning and is less stable than that of phenibut. The earlier and more stable effects of phenibut, as compared to gaboxadol, on storage in memory of the inhibitory significance of a stimulus may occur because GABABreceptors play the dominant role in the development of internal inhibition during an early stage of conditioning. On the other hand this may occur because the participation of both GABAAand GABABreceptors are essential to the process. We discuss the polyfunctionality of GABA receptors as a function of their structure and the positions of the relevant neurons in the brain as this factor can affect regulation of various types of psychological processes.


2008 ◽  
Vol 294 (6) ◽  
pp. H2712-H2720 ◽  
Author(s):  
Fanrong Yao ◽  
Colin Sumners ◽  
Stephen T. O'Rourke ◽  
Chengwen Sun

Increasing evidence indicates that both the angiotensin II (ANG II) and γ-aminobutyric acid (GABA) systems play a very important role in the regulation of blood pressure (BP). However, there is little information concerning the interactions between these two systems in the nucleus tractus solitarii (NTS). In the present study, we examined the effects of ANG II on GABAA and GABAB receptor (GAR and GBR) expression in the NTS of Sprague-Dawley rats. The direct effect of ANG II on GBR expression was determined in neurons cultured from NTS. Treatment of neuronal cultures with ANG II (100 nM, 5 h) induced a twofold increase in GBR1 expression, as detected with real-time RT-PCR and Western blots, but had no effect on GBR2 or GAR expression. In electrophysiological experiments, perfusion of neuronal cultures with the GBR agonist baclofen decreased neuronal firing rate by 39% and 63% in neurons treated with either PBS (control) or ANG II, respectively, indicating that chronic ANG II treatment significantly enhanced the neuronal response to GBR activation. In contrast, ANG II had no significant effect on the inhibitory action of the GAR agonist muscimol. In whole animal studies, intracerebroventricular infusion of ANG II induced a sustained increase in mean BP and an elevation of GBR1 mRNA and protein levels in the NTS. These results indicate that ANG II stimulates GBR expression in NTS neurons, and this could contribute to the central nervous system actions of ANG II that result in dampening of baroreflexes and elevated BP in the central actions of ANG II.


Sign in / Sign up

Export Citation Format

Share Document