共查询到20条相似文献,搜索用时 15 毫秒
1.
Trevor James Hamilton Adam Holcombe Martin Tresguerres 《Proceedings. Biological sciences / The Royal Society》2014,281(1775)
The average surface pH of the ocean is dropping at a rapid rate due to the dissolution of anthropogenic CO2, raising concerns for marine life. Additionally, some coastal areas periodically experience upwelling of CO2-enriched water with reduced pH. Previous research has demonstrated ocean acidification (OA)-induced changes in behavioural and sensory systems including olfaction, which is due to altered function of neural gamma-aminobutyric acid type A (GABAA) receptors. Here, we used a camera-based tracking software system to examine whether OA-dependent changes in GABAA receptors affect anxiety in juvenile Californian rockfish (Sebastes diploproa). Anxiety was estimated using behavioural tests that measure light/dark preference (scototaxis) and proximity to an object. After one week in OA conditions projected for the next century in the California shore (1125 ± 100 µatm, pH 7.75), anxiety was significantly increased relative to controls (483 ± 40 µatm CO2, pH 8.1). The GABAA-receptor agonist muscimol, but not the antagonist gabazine, caused a significant increase in anxiety consistent with altered Cl− flux in OA-exposed fish. OA-exposed fish remained more anxious even after 7 days back in control seawater; however, they resumed their normal behaviour by day 12. These results show that OA could severely alter rockfish behaviour; however, this effect is reversible. 相似文献
2.
Lei Ding Run Gao Xiao-Qing Xiong Xing-Ya Gao Qi Chen Yue-Hua Li Yu-Ming Kang Guo-Qing Zhu 《PloS one》2015,10(8)
Background
Chemical stimulation of white adipose tissue (WAT) induces adipose afferent reflex (AAR), and thereby causes a general sympathetic activation. Paraventricular nucleus (PVN) is important in control of sympathetic outflow. This study was designed to investigate the role of γ-aminobutyric acid (GABA) in PVN in regulating the AAR.Methodology/Principal Findings
Experiments were carried out in anesthetized rats. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded. AAR was evaluated by the RSNA and MAP responses to electrical stimulation of the right epididymal WAT (eWAT) afferent nerve. Electrical stimulation of eWAT afferent nerve increase RSNA. Bilateral microinjection of the GABAA receptor agonist isoguvacine or the GABAB receptor agonist baclofen attenuated the AAR. The effect of isoguvacine on the AAR was greater than that of baclofen. The GABAA receptor antagonist gabazine enhanced the AAR, while the GABAB receptor antagonist CGP-35348 had no significant effect on the AAR. Bilateral PVN microinjection of vigabatrin, a selective GABA-transaminase inhibitor, to increase endogenous GABA levels in the PVN abolished the AAR. The inhibitory effect of vigabatrin on the AAR was attenuated by the pretreatment with gabazine or CGP-35348. Pretreatment with combined gabazine and CGP-35348 abolished the effects of vigabatrin.Conclusions
Activation of GABAA or GABAB receptors in the PVN inhibits the AAR. Blockade of GABAA receptors in the PVN enhances the AAR. Endogenous GABA in the PVN plays an important role in regulating the AAR. 相似文献3.
Susie Andrade Bruno D. Arbo Bruna A. M. Batista Alice M. Neves Gisele Branchini Ilma S. Brum Helena M. T. Barros Rosane Gomez Maria Flavia M. Ribeiro 《Cell biochemistry and function》2012,30(8):696-700
Progesterone is a neuroactive hormone with non‐genomic effects on GABAA receptors (GABAAR). Changes in the expression of GABAAR subunits are related to depressive‐like behaviors in rats. Moreover, sex differences and depressive behaviors have been associated with prefrontal brain asymmetry in rodents and humans. Thus, our objective was to investigate the effect of progesterone on the GABAAR α1 and γ2 subunits mRNA expression in the right and left prefrontal cortex of diestrus female and male rats exposed to the forced swimming test (FST). Male and female rats (n = 8/group) were randomly selected to receive a daily dose of progesterone (0·4 mg·kg–1) or vehicle, during two complete female estrous cycles (8–10 days). On the experiment day, male rats or diestrus female rats were euthanized 30 min after the FST. Our results showed that progesterone significantly increased the α1 subunit mRNA in both hemispheres of male and female rats. Moreover, there was an inverse correlation between depressive‐like behaviors and GABAAR α1 subunit mRNA expression in the right hemisphere in female rats. Progesterone decreased the GABAAR γ2 mRNA expression only in the left hemisphere of male rats. Therefore, we conclude that the GABAA system displays an asymmetric distribution according to sex and that progesterone, at lower doses, presents an antidepressant effect after increasing the GABAAR α1 subunit expression in the right prefrontal cortex of female rats. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
4.
In rats, a single exposure to 3 MPa nitrogen induces change in motor processes, a sedative action and a decrease in dopamine
release in the striatum. These changes due to a narcotic effect of nitrogen have been attributed to a decrease in glutamatergic
control and the facilitation of GABAergic neurotransmission involving NMDA and GABAA receptors, respectively. After repeated exposure to nitrogen narcosis, a second exposure to 3 MPa increased dopamine levels
suggesting a change in the control of the dopaminergic pathway. We investigated the role of the nigral NMDA and GABAA receptors in changes in the striatal dopamine levels. Dopamine-sensitive electrodes were implanted into the striatum under
general anesthesia, together with a guide-cannula for drug injections into the SNc. Dopamine level was monitored by in vivo
voltammetry. The effects of NMDA/GABAA receptor agonists (NMDA/muscimol) and antagonists (AP7/gabazine) on dopamine levels were investigated. Rats were exposed
to 3 MPa nitrogen before and after five daily exposures to 1 MPa. After these exposures to nitrogen narcosis, gabazine, NMDA
and AP7 had no effect on the nitrogen-induced increase in dopamine levels. By contrast, muscimol strongly enhanced the increase
in dopamine level induced by nitrogen. Our findings suggest that repeated nitrogen exposure disrupted NMDA receptor function
and decreased GABAergic input by modifying GABAA receptor sensitivity. These findings demonstrated a change in the mechanism of action of nitrogen at pressure. 相似文献
5.
Y Yanovsky SR Schubring Q Yao Y Zhao S Li A May HL Haas JS Lin OA Sergeeva 《PloS one》2012,7(8):e42512
Since ancient times ursodeoxycholic acid (UDCA), a constituent of bile, is used against gallstone formation and cholestasis. A neuroprotective action of UDCA was demonstrated recently in models of Alzheimer''s disease and retinal degeneration. The mechanisms of UDCA action in the nervous system are poorly understood. We show now that UDCA promotes wakefulness during the active period of the day, lacking this activity in histamine-deficient mice. In cultured hypothalamic neurons UDCA did not affect firing rate but synchronized the firing, an effect abolished by the GABAAR antagonist gabazine. In histaminergic neurons recorded in slices UDCA reduced amplitude and duration of spontaneous and evoked IPSCs. In acutely isolated histaminergic neurons UDCA inhibited GABA-evoked currents and sIPSCs starting at 10 µM (IC50 = 70 µM) and did not affect NMDA- and AMPA-receptor mediated currents at 100 µM. Recombinant GABAA receptors composed of α1, β1–3 and γ2L subunits expressed in HEK293 cells displayed a sensitivity to UDCA similar to that of native GABAA receptors. The mutation α1V256S, known to reduce the inhibitory action of pregnenolone sulphate, reduced the potency of UDCA. The mutation α1Q241L, which abolishes GABAAR potentiation by several neurosteroids, had no effect on GABAAR inhibition by UDCA. In conclusion, UDCA enhances alertness through disinhibition, at least partially of the histaminergic system via GABAA receptors. 相似文献
6.
Spreading depolarization (SD) is a slowly propagating wave of near complete depolarizations of neurons and glia. Previous studies have reported large GABA releases during SD, but there is limited understanding of how GABA release and receptor activation are regulated and influence the propagating SD wavefront, as well as an excitatory phase immediately following the passage of SD. The present study characterized GABA-A type receptor (GABAAR) currents during SD generated by KCl microinjection in acute hippocampal slices from adult mice. Spontaneous GABAAR-mediated currents (sIPSCs) were initially enhanced, and were followed by a large outward current at the wavefront. sIPSC were then transiently supressed during the late SD phase, resulting in a significant reduction of the sIPSC/sEPSC ratio. The large outward current generated during SD was eliminated by the GABAAR antagonist gabazine, but the channel potentiator/agonist propofol failed to potentiate the current, likely because of a ceiling effect. Extracellular Cl− decreases recorded during SD were reduced by the antagonist but were not increased by the potentiator. Together with effects of GABAAR modulators on SD propagation rate, these results demonstrate a significant inhibitory role of the initial GABAAR activation and suggest that intracellular Cl− loading is insufficient to generate excitatory GABAAR responses during SD propagation. These results provide a mechanistic explanation for facilitating effects of GABAAR antagonists, and the lack of inhibitory effect of GABAAR potentiators on SD propagation. In addition, selective suppression of GABA transmission in the late SD period and the lack of effect of GABAA modulators on the duration of SD suggests that GABA modulation may not be effective approach to protect neurons during the vulnerable phase of SD. 相似文献
7.
Iqbal F Ellwood R Mortensen M Smart TG Baker JR 《Bioorganic & medicinal chemistry letters》2011,21(14):4252-4254
A selection of highly potent analogues based on the gabazine structure is described. Their syntheses are carried out in just four steps, and their potencies for antagonism at the GABAA receptor were measured. All antagonists showed significantly higher potencies compared to the parent competitive antagonist, gabazine. 相似文献
8.
Effect of avermectin (AVM) on the expression of γ‐aminobutyric acid A receptor (GABAAR) in Carassius gibelio (Bloch, 1782)
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A. L. Zhou K. Hu J. M. Ruan H. P. Cao Y. Wang Y. N. Zhao X. L. Yang 《Zeitschrift fur angewandte Ichthyologie》2015,31(5):862-869
This study describes the effect of avermectin (AVM) on the expression of γ‐aminobutyric acid A receptor (GABAAR) in Carassius gibelio. To assess the specific expression of GABAAR in the brain, gonads, liver, kidneys, heart, muscles, and skin of C. gibelio, the expression of GABAAR α1 subunit (GABAARα1) was measured by Western blotting. To study the effects of AVM on the expression of GABAAR, the median lethal concentration (LC50) at 24, 48, and 96 h of AVM was determined and the expression of GABAAR in the brain, liver, and kidneys of the corresponding C. gibelio evaluated by Western blotting and immunohistochemistry. The results show that GABAAR was expressed in the brain, gonads, liver, kidneys, heart, intestines, muscles, and skin, while primarily distributed in the central nervous system and moderately distributed in peripheral tissues. The expression of GABAAR in the brain, liver, and kidney tissues of C. gibelio was increased with the treatment of AVM at 24 h LC50, but attenuated by the treatment of AVM at 48 h LC50 and 96 h LC50. This suggests a threshold effect of AVM. 相似文献
9.
Phylogenetic studies suggest that GABA and glycine receptors derive, as a result of divergent evolution, from a common ancestral
protoreceptor originated in a unicellular organism. This raises the possibility that members of the ligand-gated ion channels
(LGIC) superfamily might be widely present in living organisms including bacteria and primitive invertebrates. High-affinity
GABA receptors occur in the tissues of Hydra vulgaris whose pharmacological characteristics compare with those of mammalian ionotropic GABA receptors. Behavioural studies have
shown that activation of these GABA
A
-like receptors by their allosteric modulators increases the duration of response to reduced glutathione (GSH). Recently,
strychnine-sensitive glycine receptors have been shown to occur in Hydra tissues. Activation of these glyR also results in increased duration of the response to GSH. In order to investigate the
contribution of endogenous transmitters to the modulation of the feeding response, we studied the effects of exposing the
polyps to brief depolarizing pulses prior to the GSH test. A severe inhibition of the response was observed following exposure
to KCl or veratridine. Administration of GABA or muscimol counteracted the effects of the pulses in a dose-dependent manner.
The effects of GABA or muscimol were suppressed by the GABA
A
-specific antagonist gabazine both in pulse-untreated and treated polyps. By contrast, glycine and its agonist taurine were
not able to restore the physiological duration of response in pulse-treated Hydra, while another glyR agonist, β-alanine, partially reduced the pulse-induced inhibition. We conclude that GABA appears to
be the major inhibitory transmitter responsible for the regulation of the feeding response. Molecular studies aimed at identifying
GABA receptor subunits are in progress. 相似文献
10.
Background
A proportion of small diameter primary sensory neurones innervating human skin are chemosensitive. They respond in a receptor dependent manner to chemical mediators of inflammation as well as naturally occurring algogens, thermogens and pruritogens. The neurotransmitter GABA is interesting in this respect because in animal models of neuropathic pain GABA pre-synaptically regulates nociceptive input to the spinal cord. However, the effect of GABA on human peripheral unmyelinated axons has not been established.Methodology/Principal Findings
Electrical stimulation was used to assess the effect of GABA on the electrical excitability of unmyelinated axons in isolated fascicles of human sural nerve. GABA (0.1–100 µM) increased electrical excitability in a subset (ca. 40%) of C-fibres in human sural nerve fascicles suggesting that axonal GABA sensitivity is selectively restricted to a sub-population of human unmyelinated axons. The effects of GABA were mediated by GABAA receptors, being mimicked by bath application of the GABAA agonist muscimol (0.1–30 µM) while the GABAB agonist baclofen (10–30 µM) was without effect. Increases in excitability produced by GABA (10–30 µM) were blocked by the GABAA antagonists gabazine (10–20 µM), bicuculline (10–20 µM) and picrotoxin (10–20 µM).Conclusions/Significance
Functional GABAA receptors are present on a subset of unmyelinated primary afferents in humans and their activation depolarizes these axons, an effect likely due to an elevated intra-axonal chloride concentration. GABAA receptor modulation may therefore regulate segmental and peripheral components of nociception. 相似文献11.
S. SanMartin F. Andrés-Trelles L. Menendez A. Meana A. Hidalgo A. Baamonde 《Cellular and molecular neurobiology》1996,16(3):427-431
Summary GABAA agonists do not respond to the same degree to allosteric modulators of the GABAA receptor complex such as benzodiazepines. We report there the effects of two steroids (alfaxalone and pregnenolone sulfate) on the inhibition induced by two GABAA agonists, 3-amino propane sulphonic acid (3-APS) and muscimol, on the extracellular evoked potentials obtained in CA1 of mice hippocampi. Alfaxalone (1µM) potentiates the effects of both agonists, although incubation times longer than 15 minutes are required to potentiate the inhibitory effect of muscimol. Lower doses of pregnenolone sulfate at shorter incubation periods are able to inhibit the effects produced by single doses of 3-APS as compared to muscimol (15µM during 5 minvs 30µM during 5 min). Our results confirm the possibility that there might be differences in the interaction between GABAA agonists and modulatory steroids. 相似文献
12.
N-Acetylaspartylglutamate Stimulates Metabotropic Glutamate Receptor 3 to Regulate Expression of the GABAA α6 Subunit in Cerebellar Granule Cells 总被引:1,自引:1,他引:0
Subroto Ghose Barbara Wroblewska Lorenzo Corsi †Dennis R. Grayson ‡Angel L. De Blas Stefano Vicini Joseph H. Neale 《Journal of neurochemistry》1997,69(6):2326-2335
Abstract: We have shown that the vertebrate neuropeptide N-acetylaspartylglutamate (NAAG) meets the criteria for a neurotransmitter, including function as a selective metabotropic glutamate receptor (mGluR) 3 agonist. Short-term treatment of cerebellar granule cells with NAAG (30 µM) results in the transient increase in content of GABAAα6 subunit mRNA. Using quantitative PCR, this increase was determined to be up to 170% of control values. Similar effects are seen following treatment with trans-1-aminocyclopentane-1,3-dicarboxylate and glutamate and are blocked by the mGluR antagonists (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl)glycine and (2S)-α-ethylglutamic acid. The effect is pertussis toxin-sensitive. The increase in α6 subunit mRNA level can be simulated by activation of other receptors negatively linked to adenylate cyclase activity, such as adenosine A1, α2-adrenergic, muscarinic, and GABAB receptors. Forskolin stimulation of cyclic AMP (cAMP) levels abolished the effect of NAAG. The change in α6 levels induced by 30 µM NAAG can be inhibited in a dose-dependent manner by simultaneous application of increasing doses of the β-adrenergic receptor agonist isoproterenol. The increase in α6 mRNA content is followed by a fourfold increase in α6 protein level 6 h posttreatment. Under voltage-clamped conditions, NAAG-treated granule cells demonstrate an increase in the furosemide-induced inhibition of GABA-gated currents in a concentration-dependent manner, indicating an increase in functional α6-containing GABAA receptors. These data support the hypothesis that NAAG, acting through mGluR3, regulates expression of the GABAAα6 subunit via a cAMP-mediated pathway and that cAMP-coupled receptors for other neurotransmitters may similarly influence GABAA receptor subunit composition. 相似文献
13.
Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of
other types of channels, a process called cross-talk. The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABAA receptor) are important excitatory and inhibitory receptors in the central nervous system, respectively. Currently, cross-talk
between the NMDA receptor and the GABAA receptor, particularly in the central auditory system, is not well understood. In the present study, we investigated functional
interactions between the NMDA receptor and the GABAA receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus, which is an important
nucleus in the central auditory system. We found that the currents induced by aspartate at 100 μmol L−1 were suppressed by the pre-perfusion of GABA at 100 μmol L−1, indicating cross-inhibition of NMDA receptors by activation of GABAA receptors. Moreover, we found that the currents induced by GABA at 100 μmol L−1 (I
GABA) were not suppressed by the pre-perfusion of 100 μmol L−1 aspartate, but those induced by GABA at 3 μmol L−1 were suppressed, indicating concentration-dependent cross-inhibition of GABAA receptors by activation of NMDA receptors. In addition, inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca2+ channels with CdCl2 in a solution that contained Ca2+, however, CdCl2 effectively attenuated the inhibition of I
GABA by aspartate when it was perfused in a solution that contained Ba2+ instead of Ca2+ or a solution that contained Ca2+ and 10 mmol L−1 BAPTA, a membrane-permeable Ca2+ chelator, suggesting that this inhibition is mediated by Ca2+ influx through NMDA receptors, rather than voltage-dependent Ca2+ channels. Finally, KN-62, a potent inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII), reduced the inhibition of I
GABA by aspartate, indicating the involvement of CaMKII in this cross-inhibition. Our study demonstrates a functional interaction
between NMDA and GABAA receptors in the inferior colliculus of rats. The presence of cross-talk between these receptors suggests that the mechanisms
underlying information processing in the central auditory system may be more complex than previously believed. 相似文献
14.
We studied the effect of furosemide on GABAA-induced 36Cl transport and GABAA-induced Cl--ATPase activity in synaptic membranes of fish brain. At physiological pH 7.4, GABA (0.1–100 µM) stimulated 36Cl influx in synaptoneurosomes and Cl--ATPase activity in synaptic membranes. Furosemide (0.1–0.5 mM) removed the activating effect of the mediator on chloride transport and enzyme activity (I50 equaled 0.16 and 0.12 mM, respectively). In the absence of the mediator, picrotoxin (50 µM) activated the basal 36Cl influx in synaptoneurosomes and the basal Mg2+-ATPase activity of synaptic membranes. Furosemide (1 mM) removed the activating effect of picrotoxin on both biochemical processes. The obtained data demonstrated similar sensitivities of GABAA-induced transport of 36Cl in synaptoneurosomes and of GABAA-induced Cl--ATPase activity in the synaptic membranes to furosemide and indicated the involvement of the ATPase in GABAA-induced processes. The soluble ATPase, recovered by sodium deoxycholate solubilization of the membranes, remained sensitive to GABAA-ergic ligands, which suggested proximity of their binding sites with ATP hydrolysis sites in the protein molecule and their structural coupling.Translated from Izvestiya Akademii Nauk, Seriya Biologicheskaya, No. 1, 2005, pp. 18–22.Original Russian Text Copyright © 2005 by Menzikov, Menzikova. 相似文献
15.
Oxidative respiration is strongly temperature driven. However, in woody stems, efflux of CO2 to the atmosphere (E
A), commonly used to estimate the rate of respiration (R
S), and stem temperature (T
st) have often been poorly correlated, which we hypothesized was due to transport of respired CO2 in xylem sap, especially under high rates of sap flow (f
s). To test this, we measured E
A, T
st, f
s and xylem sap CO2 concentrations ([CO2*]) in 3-year-old Populus deltoides trees under different weather conditions (sunny and rainy days) in autumn. We also calculated R
S by mass balance as the sum of both outward and internal CO2 fluxes and hypothesized that R
S would correlate better with T
st than E
A. We found that E
A sometimes correlated well with T
st, but not on sunny mornings and afternoons or on rainy days. When the temperature effect on E
A was accounted for, a clear positive relationship between E
A and xylem [CO2*] was found. [CO2*] varied diurnally and increased substantially at night and during periods of rain. Changes in [CO2*] were related to changes in f
s but not T
st. We conclude that changes in both respiration and internal CO2 transport altered E
A. The dominant component flux of R
S was E
A. However, on a 24-h basis, the internal transport flux represented 9–18% and 3–7% of R
S on sunny and rainy days, respectively, indicating that the contribution of stem respiration to forest C balance may be larger
than previously estimated based on E
A measurements. Unexpectedly, the relationship between R
S and T
st was sometimes weak in two of the three trees. We conclude that in addition to temperature, other factors such as water deficits
or substrate availability exert control on the rate of stem respiration so that simple temperature functions are not sufficient
to predict stem respiration. 相似文献
16.
S. V. Ovsepyan N. P. Vesselkin 《Journal of Evolutionary Biochemistry and Physiology》2002,38(6):743-754
The role of GABAA- and GABAB-receptors in presynaptic inhibition of primary afferent fibers was studied on an isolated preparation of the spinal cord of the frog Rana ridibunda. It is shown that the inhibitory effect of GABA on synaptic transmission from afferent fiber to motoneuron is caused by activation of both GABAA- and GABAB-receptors. A temporal correlation (± 5 min) was shown between the blocking action of bicuculline (a specific antagonist of GABAA-receptors) on primary afferent fiber depolarization (PAD) and its potentiating effect on the excitatory postsynaptic potential (EPSP) at parallel intracellular recording of EPSP in motoneuron and PAD in axons of the dorsal root. As a basis of this correlation, the single GABAA-receptor mechanism is discussed, which mediates the effect of bicuculline on PAD and EPSP. When a specific agonist of GABAB-receptor, baclofen, and an antagonist of GABAB-receptor, 2(OH)-saclofen, were applied, the obtained data indicated an involvement of GABAB-receptors in inhibition of synaptic transmission from afferent fibers to the motoneuron. Analysis of parameters of the unitary synaptic responses recorded in the control experiments and of their changes under the effect of (– )-baclofen indicates that the inhibitory action caused by activation of GABAB-receptors develops at the presynaptic level. 相似文献
17.
18.
《Cell cycle (Georgetown, Tex.)》2013,12(18):2985-2995
Previous research indicates that the GABAAergic system is involved in the pathophysiology of the fragile X syndrome, a frequent form of inherited intellectual disability and associated with autism spectrum disorder. However, the molecular mechanism underlying GABAAergic deficits has remained largely unknown. Here, we demonstrate reduced mRNA expression of GABAA receptor subunits in the cortex and cerebellum of young Fmr1 knockout mice. In addition, we show that the previously reported underexpression of specific subunits of the GABAA receptor can be corrected in YAC transgenic rescue mice, containing the full-length human FMR1 gene in an Fmr1 knockout background. Moreover, we demonstrate that FMRP directly binds several GABAA receptor mRNAs. Finally, positive allosteric modulation of GABAA receptors with the neurosteroid ganaxolone can modulate specific behaviors in Fmr1 knockout mice, emphasizing the therapeutic potential of the receptor. 相似文献
19.
Darren Goffin Johan Aarum Jörn E. Schroeder Jasmina N. Jovanovic Tsu Tshen Chuang 《Journal of neurochemistry》2008,107(4):964-975
The proliferation and differentiation of neural progenitor (NP) cells can be regulated by neurotransmitters including GABA and dopamine. The present study aimed to examine how these two neurotransmitter systems interact to affect post‐natal hippocampal NP cell proliferation in vitro. Mouse hippocampal NP cells express functional GABAA receptors, which upon activation led to an increase in intracellular calcium levels via the opening of L‐type calcium channels. Activation of these GABAA receptors also caused a significant decrease in proliferation; an effect that required the entry of calcium through L‐type calcium channels. Furthermore, while activation of D1‐like dopamine receptors had no effect on proliferation, it abrogated the suppressive effects of GABAA receptor activation on proliferation. The effects of D1‐like dopamine receptors are associated with a decrease in the ability of GABAA receptors to increase intracellular calcium levels, and a reduction in the surface expression of GABAA receptors. In this way, D1‐like dopamine receptor activation can increase the proliferation of NP cells by preventing GABAA receptor‐mediated inhibition of proliferation. These results suggest that, in conditions where NP cell proliferation is under the tonic suppression of GABA, agonists which act through D1‐like dopamine receptors may increase the proliferation of neural progenitors. 相似文献
20.
《Journal of receptor and signal transduction research》2013,33(1-3):99-113
AbstractThe experiments reported here were motivated by our interest to express in stably-transfected cells large amounts of recombinant rat GABAA receptors. For this, we developed an original two step selection strategy, in which the first step consisted of transfecting HEK 293 cells with rat GABAA receptor α and β subunits. G 418 resistant colonies isolated at this step were screened for [3H] muscimol binding to select for those that coexpressed α- and β-subunits. The best α and β subunit expressing colony was then supertransfected with a plasmid coding for the γ rat GABAA receptor subunit and a mutant DHFR gene. After a second round of selection, this time in presence of methotrexate, those colonies that coexpressed ternary αβγ GABAA receptor combinations were distinguished using [3H] flumazenil as a probe. This strategy was applied to the isolation of 3 GABAA receptor clones, α1β2γ2S, α1β2γ2S and α1β2γ2S, that expressed relatively high levels of these proteins. These 3 cell lines exhibited pharmacological and functional properties similar to cells transiently-transfected with equivalent subunit combinations. These cell lines therefore provide attractive models with which to evaluate the intrinsic activity and potency of compounds at recombinant GABAA receptor subtypes. 相似文献