共查询到20条相似文献,搜索用时 0 毫秒
1.
Liu J Wang F Huang C Long LH Wu WN Cai F Wang JH Ma LQ Chen JG 《Cellular and molecular neurobiology》2009,29(3):317-328
Recent evidences indicate the existence of an atypical D1 dopamine receptor other than traditional D1 dopamine receptor in the brain that mediates PI hydrolysis via activation of phospholipase Cβ (PLCβ). To further understand the basic physiological function of this receptor in brain, the effects of a selective phosphoinositide
(PI)-linked D1 dopamine receptor agonist SKF83959 on cytosolic free calcium concentration ([Ca2+]i) in cultured rat prefrontal cortical astrocytes were investigated by calcium imaging. The results indicated that SKF83959
caused a transient dose-dependent increase in [Ca2+]i. Application of D1 receptor, but not D2, α1 adrenergic, 5-HT receptor, or cholinergic antagonist prevented SKF83959-induced [Ca2+]i rise, indicating that activation of the D1 dopamine receptor was essential for this response. Increase in [Ca2+]i was a two-step process characterized by an initial increase in [Ca2+]i mediated by release from intracellular stores, supplemented by influx through voltage-gated calcium channels, receptor-operated
calcium channels, and capacitative Ca2+ entry. Furthermore, SKF83959-stimulated increase in [Ca2+]i was abolished following treatment with a PLC inhibitor. Overall, these results suggested that activation of D1 receptor by SKF83959 mediates a dose-dependent mobilization of [Ca2+]i via the PLC signaling pathway in cultured rat prefrontal cortical astrocytes. 相似文献
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Nicotine is a highly addictive drug and exerts this effect partially through the modulation of dopamine release and increasing extracellular dopamine in regions such as the brain reward systems. Nicotine acts in these regions on nicotinic acetylcholine receptors. The effect of nicotine on the frequency dependent modulation of dopamine release is well established and the purpose of this study was to investigate whether dopamine D1 receptor (D1R) ligands have an influence on this. Using fast cyclic voltammetry and rat corticostriatal slices, we show that D1R ligands are able to modulate the effect of nicotine on dopamine release. Nicotine (500 nM) induced a decrease in dopamine efflux at low frequency (single pulse or five pulses at 10 Hz) and an increase at high frequency (100 Hz) electrical field stimulation. The D1R agonist SKF-38393, whilst having no effect on dopamine release on its own or on the effect of nicotine upon multiple pulse evoked dopamine release, did significantly prevent and reverse the effect of nicotine on single pulse dopamine release. Interestingly similar results were obtained with the D1R antagonist SCH-23390. In this study we have demonstrated that the modulation of dopamine release by nicotine can be altered by D1R ligands, but only when evoked by single pulse stimulation, and are likely working via cholinergic interneuron driven dopamine release. 相似文献
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Boisbouvier J Bryce DL O'neil-Cabello E Nikonowicz EP Bax A 《Journal of biomolecular NMR》2004,30(3):287-301
New methods are described for accurate measurement of multiple residual dipolar couplings in nucleic acid bases. The methods use TROSY-type pulse sequences for optimizing resolution and sensitivity, and rely on the E.COSY principle to measure the relatively small two-bond 2DCH couplings at high precision. Measurements are demonstrated for a 24-nt stem-loop RNA sequence, uniformly enriched in 13C, and aligned in Pf1. The recently described pseudo-3D method is used to provide homonuclear 1H-1H decoupling, which minimizes cross-correlation effects and optimizes resolution. Up to seven 1H-13C and 13C-13C couplings are measured for pyrimidines (U and C), including 1DC5H5, 1DC6H6, 2DC5H6, 2DC6H5, 1DC5C4, 1DC5C6, and 2DC4H5. For adenine, four base couplings (1DC2H2, 1DC8H8, 1DC4C5, and 1DC5C6) are readily measured whereas for guanine only three couplings are accessible at high relative accuracy (1DC8H8, 1DC4C5, and 1DC5C6). Only three dipolar couplings are linearly independent in planar structures such as nucleic acid bases, permitting cross validation of the data and evaluation of their accuracies. For the vast majority of dipolar couplings, the error is found to be less than ±3% of their possible range, indicating that the measurement accuracy is not limiting when using these couplings as restraints in structure calculations. Reported isotropic values of the one- and two-bond J couplings cluster very tightly for each type of nucleotide. 相似文献
6.
Glutathione (γ-glutamylcysteinylglycine, GSH and oxidized glutathione, GSSG), may function as a neuromodulator at the glutamate
receptors and as a neurotransmitter at its own receptors. We studied now the effects of GSH, GSSG, glutathione derivatives
and thiol redox agents on the spontaneous, K+- and glutamate-agonist-evoked releases of [3H]dopamine from mouse striatal slices. The release evoked by 25 mM K+ was inhibited by GSH, S-ethyl-, -propyl-, -butyl- and pentylglutathione and glutathione sulfonate. 5,5′-Dithio-bis-2-nitrobenzoate (DTNB) and l-cystine were also inhibitory, while dithiothreitol (DTT) and l-cysteine enhanced the K+-evoked release. Ten min preperfusion with 50 μM ZnCl2 enhanced the basal unstimulated release but prevented the activation of K+-evoked release by DTT.
Kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) evoked dopamine release but the other glutamate receptor
agonists N-methyl-d-aspartate (NMDA), glycine (1 mM) and trans-1-aminocyclopentane-1,3-dicarboxylate (t-ACPD, 0.5 mM), and the modulators GSH, GSSG, glutathione sulfonate, S-alkyl-derivatives of glutathione, DTNB, cystine, cysteine and DTT (all 1 mM) were without effect. The release evoked by 1 mM
glutamate was enhanced by 1 mM GSH, while GSSG, glutathionesulfonate and S-alkyl derivatives of glutathione were generally without effect or inhibitory. NMDA (1 mM) evoked release only in the presence
of 1 mM GSH but not with GSSG, other peptides or thiol modulators. l-Cysteine (1 mM) enhanced the glutamate-evoked release similarly to GSH. The activation by 1 mM kainate was inhibited by S-ethyl-, -propyl-, and -butylglutathione and the activation by 0.5 mM AMPA was inhibited by S-ethylglutathione but enhanced by GSSG.
Glutathione alone does not directly evoke dopamine release but may inhibit the depolarization-evoked release by preventing
the toxic effects of high glutamate, and by modulating the cysteine–cystine redox state in Ca2+ channels. GSH also seems to enhance the glutamate-agonist-evoked release via both non-NMDA and NMDA receptors. In this action,
the γ-glutamyl and cysteinyl moieties of glutathione are involved. 相似文献
7.
Gonzalo Sánchez Natalia Colettis Pablo Vázquez Carlos Cerveñansky Alejandra Aguirre Jorge A. Quillfeldt Diana Jerusalinsky Edgar Kornisiuk 《Neurochemical research》2009,34(8):1363-1371
The five muscarinic acetylcholine receptors (M1–M5) are differentially expressed in the brain. M2 and M4 are coupled to inhibition of stimulated adenylyl cyclase, while M1, M3 and M5 are mainly coupled to the phosphoinositide pathway. We studied the muscarinic receptor regulation of adenylyl cyclase activity
in the rat hippocampus, compared to the striatum and amygdala. Basal and forskolin-stimulated adenylyl cyclase activity was
higher in the striatum but the muscarinic inhibition was much lower. Highly selective muscarinic toxins MT1 and MT2—affinity
order M1 ≥ M4 >> others—and MT3—highly selective M4 antagonist—did not show significant effects on basal or forskolin-stimulated cyclic AMP production but, like scopolamine,
counteracted oxotremorine inhibition. Since MTs have negligible affinity for M2, M4 would be the main subtype responsible for muscarinic inhibition of forskolin-stimulated enzyme. Dopamine stimulated a small
fraction of the enzyme (3.1% in striatum, 1.3% in the hippocampus). Since MT3 fully blocked muscarinic inhibition of dopamine-stimulated
enzyme, M4 receptor would be responsible for this regulation.
Diana Jerusalinsky and Edgar Kornisiuk contributed equally to this paper. 相似文献
8.
Doleviczényi Z Vizi ES Gacsályi I Pallagi K Volk B Hársing LG Halmos G Lendvai B Zelles T 《Neurochemical research》2008,33(11):2364-2372
In humans, serotonin (5-HT) has been implicated in numerous physiological and pathological processes in the peripheral auditory
system. Dopamine (DA), another transmitter of the lateral olivocochlear (LOC) efferents making synapses on cochlear nerve
dendrites, controls auditory nerve activation and protects the sensory nerve against overactivation. Using in vitro microvolume
superfusion techniques we tested 5-HT6 and 5-HT7 receptor antagonists whether they can influence dopamine (DA) release from the guinea-pig cochlea in control and in ischemic
conditions using currently available and new 5-HT6 and 5-HT7 antagonists and mixed antagonists, which were synthesized and characterized for the current study. While the 5-HT7 antagonist SB-258719 was ineffective, SB-271046, which blocks the 5-HT6 receptor, caused a significant increase in cochlear DA release what is contradictory with the excitatory nature of this type
of receptor. Moreover, the mixed 5-HT6/7 antagonist EGIS-12233 induced an even more pronounced increase in the resting DA release. To understand why the block of
an excitatory receptor results in an increase instead of a decrease in function, we investigated the possible involvement
of an indirect neural mechanism through an inhibitory system. In the presence of the GABAA receptor blocker bicuculline, EGIS-12233 failed to increase the release of DA, suggesting that the serotonin receptor modulation
of DA release from the lateral olivocochlear efferents in the cochlea was produced indirectly by decreasing the GABAergic
inhibitory tone on dopaminergic nerve endings. The mixed 5-HT7/D4 receptor antagonist EGIS-11983 significantly increased both the stimulation-evoked and the resting DA release, while the
selective D4 blocker L-741,741 alone had no significant effect. Ischemia, simulated by oxygen and glucose deprivation from
the perfusion solution had no action on the effect of the drugs. Drugs that can increase the release of DA from LOC terminals
in the cochlea may have a role in the treatment of sensorineural hearing loss. 相似文献
9.
Thaísa Godinho da Encarnação Camila Cabral Portugal Caio Eduardo Nogueira Felipe Nascimento Santiago Renato Socodato Roberto Paes-de-Carvalho 《Molecular neurobiology》2018,55(10):7858-7871
Ascorbate, the reduced form of vitamin C, is highly concentrated in the central nervous system (CNS), including the retina, where it plays important physiological functions. In the CNS, the plasma membrane transporter sodium vitamin C co-transporter 2 (SVCT2) is responsible for ascorbate transport in neurons. The neurotransmitter dopamine (DA), acting through D1- and D2-like receptor subfamilies and classically coupled to adenylyl cyclase, is known to modulate synaptic transmission in the retina. Here, we reveal that DA controls the release of ascorbate from retinal neurons. Using primary retinal cultures, we show that this DA effect is dose-dependent, occurring by the reversal of the SVCT2, and could be elicited by brief and repetitive pulses of DA. The DA effect in inducing ascorbate release occurs by the activation of D1R and is independent of PKA. Moreover, the exchange protein directly activated by cAMP type 2 (EPAC2) is present in retinal neurons and its specific knockdown using shRNAs abrogates the D1R-induced ascorbate release. Confirming the physiological relevance of this pathway, activation of D1R or EPAC2 also triggered ascorbate release ex vivo in acute preparations of the intact retina. Overall, DA plays pivotal roles in regulating ascorbate homeostasis through an unanticipated signaling pathway involving D1R/adenylyl cyclase/cAMP/EPAC2, thereby suggesting that vitamin C might fine-tune dopaminergic neurotransmission in the retina. 相似文献
10.
The three-dimensional structure of the GABA A receptor that included the ligand/agonist binding site was constructed and validated by using molecular modeling technology. Moreover, the putative binding-mode of GABA and diazepam with GABAA receptor were investigated by means of docking studies. Based on an rmsd-tolerance of 1.0 angstroms, the docking of GABA to alpha1/beta2 interface resulted in three multi-member conformational clusters and model 2 was supported by homologous sequence alignment data and experimental evidence. On the other hand, the docking of diazepam to alpha1/gamma2 interface revealed five multi-member conformational clusters in the binding site and model 1 seemed to represent the correct orientation of diazepam in the binding site. 相似文献
11.
Abstract: The adenosine A2a receptor inhibition of potassium (15 m M )-evoked GABA release from striatal nerve terminals has been examined. High extracellular calcium concentrations (4 m M ) reduced the effect of the A2a receptor agonist CGS-21680 (1 n M ). CGS-21680 inhibited GABA release in the presence of the L-type calcium channel blocker nifedipine, which itself inhibited evoked GABA release (by 16 ± 4%). ω-Conotoxin inhibited the evoked release by 45 ± 4% and prevented the action of CGS-21680. Forskolin and 8-bromo cyclic AMP both stimulated evoked GABA release at low concentrations, but at higher concentrations they abolished the inhibition by CGS-21680 without affecting the evoked release. The nonselective protein kinase inhibitor H-7 inhibited both the evoked release and the inhibition by CGS-21680, whereas the selective protein kinase A and G inhibitor HA-1004 had no effect on either evoked release or the action of CGS-21680. Pretreatment with pertussis toxin did not affect the A2a receptor-mediated inhibition. Therefore, the effect of A2a receptor stimulation was not mediated by protein kinases A or G but was inhibited by elevated cyclic AMP levels and mimicked by inhibitors of the N-type calcium channel and protein kinase C. 相似文献
12.
The ability of different receptors to mediate inhibition of cyclic AMP accumulation due to a variety of agonists was examined in rat striatal slices. In the presence of 1 mM 3-isobutyl-1-methylxanthine, dopamine D-2, muscarinic cholinergic, and opiate receptor stimulation by RU 24926, carbachol, and morphine (all at 10(-8)-10(-5) M), respectively, inhibited the increase in cyclic AMP accumulation in slices of rat striatum due to dopamine D-1 receptor stimulation by 1 microM SKF 38393. In contrast, these inhibitory agents were unable to reduce the ability of a number of other agonists, including isoprenaline, prostaglandin E1, 2-chloroadenosine, vasoactive intestinal polypeptide, and cholera toxin, to increase cyclic AMP levels in striatal slices. These results suggest that in rat striatum either dopamine D-2, muscarinic cholinergic, and opiate receptors are only functionally linked to dopamine D-1 receptors or that the D-1 and D-2 receptors linked to adenylate cyclase lie on the cells, distinct from other receptors capable of elevating striatal cyclic AMP levels. 相似文献
13.
Expósito Inmaculada Del Arco Alberto Segovia Gregorio Mora Francisco 《Neurochemical research》1999,24(7):849-856
Interactions between endogenous dopamine, glutamate, GABA, and taurine were investigated in striatum of the freely moving rat by using microdialysis. Intrastriatal infusions of the selective dopamine uptake inhibitor nomifensine (NMF) were used to increase the endogenous extracellular dopamine. NMF produced a dose-related increase in extracellular dopamine and also increased extracellular concentrations of glutamate, GABA, and taurine. Extracellular increases of dopamine were significantly correlated with extracellular increases of glutamate and GABA, but not taurine. To investigate whether the increased extracelular dopamine produced by NMF was responsible for the concomitant increase of glutamate and GABA, D1, and D2 receptor antagonists were used. Dopamine receptor antagonists D1 (SCH23390) and D2 (sulpiride) significantly attenuated the increases of glutamate and GABA produced by NMF. These data suggest that endogenous dopamine, through both D1 and D2 dopamine receptors, plays a role in releasing glutamate and GABA in striatum of the freely moving rat. 相似文献
14.
Jingdong Long Xiaolu Lei Meiyun Chen Shulei Yang Tao Sun Junwei Zeng Deqian Yu Hong Tian Xiaohong Liu 《Neurochemical research》2018,43(2):267-275
Spinal cannabinoid receptor 1 (CB1R) and purinergic P2X receptors (P2XR) play a critical role in the process of pathological pain. Both CB1R and P2XR are expressed in spinal dorsal horn (DH) neurons. It is not clear whether CB1 receptor activation modulates the function of P2X receptor channels within dorsal horn. For this reason, we observed the effect of CP55940 (cannabinoid receptor agonist) on ATP-induced Ca2+ mobilization in cultured rat DH neurons. The changes of intracellular calcium concentration ([Ca2+]i) were detected with confocal laser scanning microscopy using fluo-4/AM as a calcium fluorescent indicator. 100 μM ATP caused [Ca2+]i increase in cultured DH neurons. ATP-evoked [Ca2+]i increase in DH neurons was blocked by chelating extracellular Ca2+ and P2 purinoceptor antagonist PPADS. At the same time, ATP-γ-S (a non-hydrolyzable ATP analogue) mimicked the ATP action, while P2Y receptor agonist ADP failed to evoke [Ca2+]i increase in cultured DH neurons. These data suggest that ATP-induced [Ca2+]i elevation in cultured DH neurons is mediated by P2X receptor. Subsequently, we noticed that, in cultured rat DH neurons, ATP-induced Ca2+ mobilization was inhibited after pretreated with CP55940 with a concentration-dependent manner, which implies that the opening of P2X receptor channels are down-regulated by activation of cannabinoid receptor. The inhibitory effect of CP55940 on ATP-induced Ca2+ response was mimicked by ACEA (CB1R agonist), but was not influenced by AM1241 (CB2R agonist). Moreover, the inhibitory effect of CP55940 on ATP-induced Ca2+ mobilization was blocked by AM251 (CB1 receptor antagonist), but was not influenced by AM630 (CB2 receptor antagonist). In addition, we also observed that forskolin (an activator of adenylate cyclase) and 8-Br-cAMP (a cell-permeable cAMP analog) reversed the inhibitory effect of CP55940, respectively. In a summary, our observations raise a possibility that CB1R rather than CB2R can downregulate the opening of P2X receptor channels in DH neurons. The reduction of cAMP/PKA signaling is a key element in the inhibitory effect of CB1R on P2X-channel-induced Ca2+ mobilization. 相似文献
15.
Valentina Giorgio Elena Bisetto Raffaella Franca David A. Harris Sabina Passamonti Giovanna Lippe 《Journal of bioenergetics and biomembranes》2010,42(2):117-123
Rat liver plasma membranes contain FOF1 complexes (ecto-FOF1) displaying a similar molecular weight to the mitochondrial FOF1 ATP synthase, as evidenced by Blue Native PAGE. Their ATPase activity was stably reduced in short-term extra-hepatic cholestasis.
Immunoblotting and immunoprecipitation analyses demonstrated that the reduction in activity was not due to a decreased expression
of ecto-FOF1 complexes, but to an increased level of an inhibitory protein, ecto-IF1, bound to ecto-FOF1. Since cholestasis down regulates the hepatic uptake of HDL-cholesterol, and ecto-FOF1 has been shown to mediate SR-BI-independent hepatic uptake of HDL-cholesterol, these findings provide support to the hypothesis
that ecto-FOF1 contributes to the fine control of reverse cholesterol transport, in parallel with SR-BI. No activity change of the mitochondrial
FOF1 ATP synthase (m-FOF1), or any variation of its association with m-IF1 was observed in cholestasis, indicating that ecto-IF1 expression level is modulated independently from that of ecto-FOF1, m-IF1 and m-FOF1. 相似文献
16.
Trincavelli ML Cuboni S Montali M Santaguida S Lucacchini A Martini C 《Neurochemical research》2008,33(7):1292-1300
Adaptive changes in serotonergic 5HT1 receptor signalling are believed to underlie the therapeutic effectiveness of antidepressant drugs. Since cells are continuously exposed to neurotransmitters/neuromodulators, spatially and temporally integrated, the responsiveness of a receptor system is dependent upon the physio-pathological state of the cell and the interaction between different neurotransmitters. In the present work, we investigated heterologous regulation of 5HT1 receptors induced by norepinephrine (NE) in human platelets. NE platelet treatment induced a time and concentration dependent 5HT1 receptor desensitisation mediated by both alpha and beta receptors through activation of intracellular protein kinases. In particular NE, through PKC activation, regulated 5HT1 receptor phosphorylation on threonine residues, causing in turn serotonin receptor-G protein uncoupling and functional responsiveness drop. These results suggest that high NE levels (released i.e. during stress disorders) may play an important role in regulating the 5HT1 responsiveness and in controlling effectiveness of drugs acting on these neurotransmitter systems. 相似文献
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Downregulation of GABAergic synaptic transmission contributes to the increase in overall excitatory activity in the ischemic brain. A reduction of GABAA receptor (GABAAR) surface expression partly accounts for this decrease in inhibitory activity, but the mechanisms involved are not fully elucidated. In this work, we investigated the alterations in GABAAR trafficking in cultured rat hippocampal neurons subjected to oxygen/glucose deprivation (OGD), an in vitro model of global brain ischemia, and their impact in neuronal death. The traffic of GABAAR was evaluated after transfection of hippocampal neurons with myc-tagged GABAAR β3 subunits. OGD decreased the rate of GABAAR β3 subunit recycling and reduced the interaction of the receptors with HAP1, a protein involved in the recycling of the receptors. Furthermore, OGD induced a calpain-mediated cleavage of HAP1. Transfection of hippocampal neurons with HAP1A or HAP1B isoforms reduced the OGD-induced decrease in surface expression of GABAAR β3 subunits, and HAP1A maintained the rate of receptor recycling. Furthermore, transfection of hippocampal neurons with HAP1 significantly decreased OGD-induced cell death. These results show a key role for HAP1 protein in the downmodulation of GABAergic neurotransmission during cerebral ischemia, which contributes to neuronal demise. 相似文献
19.
1. Insolubility of membrane constituents in nonionic detergents such as Triton X-100 has been a widely used biochemical criterion
to indicate their localization in membrane domains. However, concerns on the possibility of membrane perturbation in the presence
of detergents have led to the development of detergent-free approaches.
2. We have explored the organization of the serotonin1A receptor, an important G-protein coupled receptor, from bovine hippocampus and CHO cells using a detergent-free approach
in order to address the points of agreement with our previous results using Triton X-100.
3. A significant fraction of the serotonin1A receptor has been found to be localized in a heavy density fraction obtained using a detergent-free approach to isolate membrane
domains. In addition, we have characterized the membrane fractions isolated in terms of their lipid composition and membrane
physical properties.
4. The results obtained on the membrane localization of the serotonin1A receptor from the present experiments using a detergent-free approach correlate well with our earlier findings obtained using
a detergent-based method (Kalipatnapu, S., and Chattopadhyay, A., FEBS Lett. 576:455–460, 2004). These results provide important information on the membrane organization of the hippocampal serotonin1A receptor and are relevant in view of the concerns on the use of detergent in determination of membrane organization of constituent
proteins and lipids. 相似文献
20.
Joaquín Royo Elisa Gómez Cristina Barrero Luis Miguel Muñiz Yolanda Sanz Gregorio Hueros 《Planta》2009,230(4):807-818