共查询到20条相似文献,搜索用时 15 毫秒
1.
The effects of the endogenous cannabinoid anandamide [arachidonylethanolamide (AEA)] on the function of nicotinic acetylcholine receptor (nAChR) were investigated using the 86 Rb+ efflux assay in thalamic synaptosomes. AEA reversibly inhibited 86 Rb+ efflux induced by 300 μM ACh with an IC50 value of 0.9 ± 2 μM. Pre-treatment with the cannabinoid (CB1 ) receptor antagonist SR141716A (1 μM), the CB2 receptor antagonist SR144528 (1 μM), or pertussis toxin (0.2 mg/mL) did not alter the inhibitory effects of AEA, suggesting that known CB receptors are not involved in AEA inhibition of nAChRs. AEA inhibition of 86 Rb+ efflux was not reversed by increasing acetylcholine (ACh) concentrations. In radioligand binding studies, the specific binding of [3 H]-nicotine was not altered in the presence of AEA, indicating that AEA inhibits the function of nAChR in a non-competitive manner. Neither the amidohydrolase inhibitor phenylmethylsulfonyl fluoride (0.2 mM) nor the cyclooxygenase inhibitor, indomethacin, (5 μM) affected AEA inhibition of nAChRs, suggesting that the effect of AEA is not mediated by its metabolic products. Importantly, the extent of AEA inhibition of 86 Rb+ efflux was significantly attenuated by the absence of 1% fatty acid free bovine serum albumin pre-treatment, supporting previous findings that fatty acid-like compounds modulate the activity of nAChRs. Collectively, the results indicate that AEA inhibits the function of nAChRs in thalamic synaptosomes via a CB-independent mechanism and that the background activity of these receptors is affected by fatty acids and AEA. 相似文献
2.
Manipulation of fatty acid amide hydrolase functional activity alters sensitivity and dependence to ethanol 总被引:2,自引:0,他引:2
Vinod KY Sanguino E Yalamanchili R Manzanares J Hungund BL 《Journal of neurochemistry》2008,104(1):233-243
The aim of this study was to examine the role of fatty acid amide hydrolase (FAAH) on ethanol sensitivity, preference, and dependence. The deletion of FAAH gene or the inhibition of FAAH by carbamoyl-biphenyl-3-yl-cyclohexylcarbamate (URB597) (0.1 mg/kg) markedly increased the preference for ethanol. The study further reveals that URB597 specifically acts through FAAH and that cannabinoid-1 (CB1 ) receptor is critical for N -arachidonoyl ethanolamide (AEA) mediated ethanol-reinforced behavior as revealed by lack of URB597 effect in both FAAH and CB1 −/− mice compared with vehicle-treated −/− mice. The FAAH −/− mice displayed a lower sensitivity to hypothermic and sedative effects to acute ethanol challenge. The FAAH −/− mice also exhibited a reduction in the severity of handling-induced convulsions following withdrawal from chronic ethanol exposure. The CB1 receptor and proenkephalin gene expressions, and CB1 receptor and μ-opioid (MO) receptor-mediated G-protein activation were found to be significantly lower in the caudate-putamen, nucleus accumbens core and shell of FAAH −/− than +/+ mice. Interestingly, the MO receptor-stimulated G-protein signaling was greater in the striatum of FAAH −/− than +/+ mice following voluntary ethanol consumption. These findings suggest that an elevation in the AEA content and its action on the limbic CB1 receptor and MO receptor might contribute to ethanol-reinforced behavior. Treatment with drugs that decrease AEA tone might prove useful in reducing excessive ethanol consumption. 相似文献
3.
M. Van Der Stelt W. B. Veldhuis M. W. Wadman G. Van Zadelhoff F. Fezza G. A. Veldink J. F. G. Vliegenthart P. R. Br K. Nicolay V. Di Marzo 《Journal of neurochemistry》2003,85(Z2):6-6
The endocannabinoid anandamide (AEA) and some of its oxidative metabolites are putative ligands for the vanilloid receptor (VR1). AEA affords protection against excitotoxicity induced in vivo by ouabain, a Na+/K+‐ATPase inhibitor. This effect is only partly dependent of the cannabinoid CB1 receptor. Here, we assessed whether VR1 is involved in neuroprotection by AEA and arvanil, which is a hydrolysis‐stable ligand for both VR1 and CB1. Using magnetic resonance imaging we show that: (i) modulation of VR1, by the agonists arvanil and capsaicin and the antagonist capsazepine, leads to neuroprotective effects in the late but not acute phase after i.c. ouabain‐injection; (ii) arvanil is a potent neuroprotectant, acting at both CB1 and VR1; and (iii) the neuroprotective effects of AEA are mediated by CB1 but not by lipoxygenase metabolites or VR1. 相似文献
4.
Mato S Aso E Castro E Martín M Valverde O Maldonado R Pazos A 《Journal of neurochemistry》2007,103(5):2111-2120
Interaction between brain endocannabinoid (EC) and serotonin (5-HT) systems was investigated by examining 5-HT-dependent behavioral and biochemical responses in CB1 receptor knockout mice. CB1 knockout animals exhibited a significant reduction in the induction of head twitches and paw tremor by the 5-HT2A/C receptor selective agonist (±) DOI, as well as a reduced hypothermic response following administration of the 5-HT1A receptor agonist (±)-8-OH-DPAT. Additionally, exposure to the tail suspension test induced enhanced despair responses in CB1 knockout mice. However, the tricyclic antidepressant imipramine and the 5-HT selective reuptake inhibitor fluoxetine induced similar decreases in the time of immobility in the tail suspension test in CB1 receptor knockout and wild-type mice. No differences were found between both genotypes with regard to 5-HT2A receptor and 5-HT1A receptors levels, measured by autoradiography in different brain areas. However, a significant decrease in the ability of both, the 5-HT1A receptor agonist (±)-8-OH-DPAT and the 5-HT2A/C receptor agonist (−)DOI, to stimulate [35 S]GTPγS binding was detected in the hippocampal CA1 area and fronto-parietal cortex of CB1 receptor knockout mice, respectively. This study provides evidence that CB1 receptors are involved in the regulation of serotonergic responses mediated by 5-HT2A/C and 5-HT1A receptors, and suggests that a reduced coupling of 5-HT1A and 5-HT2A receptors to G proteins might be involved in these effects. 相似文献
5.
Maria Teresa Tebano Alberto Martire Valentina Chiodi Rita Pepponi Antonella Ferrante Maria Rosaria Domenici Claudio Frank Jiang-Fan Chen† Catherine Ledent‡ Patrizia Popoli 《Journal of neurochemistry》2009,110(6):1921-1930
Adenosine A2A , cannabinoid CB1 and metabotropic glutamate 5 (mGlu5 ) receptors are all highly expressed in the striatum. The aim of the present work was to investigate whether, and by which mechanisms, the above receptors interact in the regulation of striatal synaptic transmission. By extracellular field potentials (FPs) recordings in corticostriatal slices, we demonstrated that the ability of the selective type 1 cannabinoid receptor (CB1 R) agonist WIN55,212-2 to depress synaptic transmission was prevented by the pharmacological blockade or the genetic inactivation of A2A Rs. Such a permissive effect of A2A Rs towards CB1 Rs does not seem to occur pre-synaptically as the ability of WIN55,212-2 to increase the R2/R1 ratio under a protocol of paired-pulse stimulation was not modified by ZM241385. Furthermore, the effects of WIN55,212-2 were reduced in slices from mice lacking post-synaptic striatal A2A Rs. The selective mGlu5 R agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) potentiated the synaptic effects of WIN55,212-2, and such a potentiation was abolished by A2A R blockade. Unlike the synaptic effects, the ability of WIN55,212-2 to prevent NMDA-induced toxicity was not influenced by ZM241385. Altogether, these results show that the state of activation of A2A Rs regulates the synaptic effects of CB1 Rs and that A2A Rs may control CB1 effects also indirectly, namely through mGlu5 Rs. 相似文献
6.
Ester Aso Thibault Renoir† Guadalupe Mengod‡ Catherine Ledent§ Michel Hamon† Rafael Maldonado¶ Laurence Lanfumey† Olga Valverde 《Journal of neurochemistry》2009,109(3):935-944
Serotonergic and endocannabinoid systems are important substrates for the control of emotional behaviour and growing evidence show an involvement in the pathophysiology of mood disorders. In the present study, the absence of the activity of the CB1 cannabinoid receptor impaired serotonergic negative feedback in mice. Thus, in vivo microdialysis experiments revealed increased basal 5-HT extracellular levels and attenuated fluoxetine-induced increase of 5-HT extracellular levels in the prefrontal cortex of CB1 knockout compared with wild-type mice. These observations could be related to the significant reduction in the 5-HT transporter binding site density detected in frontal cortex and hippocampus of CB1 knockout mice. The lack of CB1 receptor also altered some 5-HT receptors related to the 5-HT feedback. Extracellular recordings in the dorsal raphe nucleus (DRN) revealed that the genetic and pharmacological blockade of CB1 receptor induced a 5-HT1A autoreceptor functional desensitization. In situ hybridization studies showed a reduction in the expression of the 5-HT2C receptor within several brain areas related to the control of the emotional responses, such as the DRN, the nucleus accumbens and the paraventricular nucleus of the hypothalamus, whereas an over-expression was observed in the CA3 area of the ventral hippocampus. These results reveal that the lack of CB1 receptor induces a facilitation of the activity of serotonergic neurons in the DRN by altering different components of the 5-HT feedback as well as an increase in 5-HT extracellular levels in the prefrontal cortex in mice. 相似文献
7.
Agonists stimulate cannabinoid 1 receptor (CB1 R) internalization. Previous work suggests that the extreme carboxy-terminus of the receptor regulates this internalization – likely through the phosphorylation of serines and threonines clustered within this region. While truncation of the carboxy-terminus (V460Z CB1 ) and consequent removal of these putative phosphorylation sites prevents endocytosis in AtT20 cells, the residues necessary for CB1 R internalization remain elusive. To determine the structural requirements for internalization, we evaluated endocytosis of carboxy-terminal mutant CB1 Rs stably expressed in HEK293 cells. In contrast to AtT20 cells, V460Z CB1 R expressed in HEK293 cells internalized to the same extent and with similar kinetics as the wild-type receptor. However, mutation of serine and/or threonine residues within the extreme carboxy-terminal attenuated internalization when these receptors were expressed in HEK293 cells. These results establish that the extreme carboxy-terminal phosphorylation sites are not required for internalization of truncated receptors, but are required for internalization of full-length receptors in HEK293 cells. Analysis of β-arrestin-2 recruitment to mutant CB1 R suggests that putative carboxy-terminal phosphorylation sites mediate β-arrestin-2 translocation. This study indicates that the local cellular environment affects the structural determinants of CB1 R internalization. Additionally, phosphorylation likely regulates the internalization of (full-length) CB1 Rs. 相似文献
8.
9.
Antonio Rodríguez-Gaztelumendi Mª Luisa Rojo Angel Pazos Alvaro Díaz 《Journal of neurochemistry》2009,108(6):1423-1433
Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed in human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases in both CB1 receptor density ([3 H]CP55490 binding) and functionality (stimulation of [35 S]GTPγS binding by the cannabinoid (CB) agonist WIN 55212-2) at the prefrontal cortex (PFC). After chronic treatment with fluoxetine (10 mg/kg/day, 14 days, s.c.), OBX-induced hyperactivity in the open-field test was fully abolished. Interestingly, chronic fluoxetine fully reversed the enhanced CB1 -receptor signaling in PFC observed following OBX. The CB agonist Δ9 -tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did not produce any behavioral effect in sham-operated animals but returned locomotor activity to control values in OBX rats. As both acute administration of Δ9 -tetrahydrocannabinol and chronic fluoxetine elicited a similar behavioral effect in the OBX rat, it is not unlikely that the regionally selective enhancement of CB1 receptor-signaling in the PFC could be related with the altered OBX behavior. Our findings reinforce the utility of this animal model to further investigating the implication of the endocannabinoid system in the modulation of emotional processes and its potential role in the adaptive responses to chronic antidepressants. 相似文献
10.
The psychoactive ingredient of marijuana, Δ9 -tetrahydrocannabinol (Δ9 -THC), can evoke apoptosis in cultured cortical neurones. Whilst the intracellular mechanisms responsible for this apoptotic pathway remain to be fully elucidated, we have recently identified a role for the CB1 type of cannabinoid (CB) receptor and the tumour suppressor protein, p53. In the current study, we demonstrate the Δ9 -THC promotes a significant increase in lysosomal permeability in a dose- and time-dependent manner. The increase in lysosomal permeability was blocked by the CB1 receptor antagonist, AM251. Δ9 -THC increased the localization of phospho-p53Ser15 at the lysosome and stimulated the release of the lysosomal cathepsin enzyme, cathepsin-D, into the cytosol. The p53 inhibitor, pifithrin-α and small interfering RNA-mediated knockdown of p53 prevented the Δ9 -THC-mediated increase in lysosomal permeability. Furthermore, the Δ9 -THC -mediated induction of apoptosis was abrogated by a cell-permeable cathepsin-D inhibitor (10 μM). Thus, the study demonstrates that Δ9 -THC impacts on the lysosomal system, via p53, to evoke lysosomal instability as an early event in the apoptotic cascade. This provides evidence for a novel link between the CB1 receptor and the lysosomal branch of the apoptotic pathway which is crucial in regulating neuronal viability following exposure to Δ9 -THC. 相似文献
11.
Accumulation of N-Arachidonoylethanolamine (Anandamide) into Cerebellar Granule Cells Occurs via Facilitated Diffusion 总被引:3,自引:1,他引:2
Cecilia J. Hillard William S. Edgemond Abbas Jarrahian William B. Campbell 《Journal of neurochemistry》1997,69(2):631-638
Abstract: N -Arachidonoylethanolamine (anandamide, AEA) is a putative endogenous ligand of the cannabinoid receptor. Intact cerebellar granule neurons in primary culture rapidly accumulate AEA. [3 H]AEA accumulation by cerebellar granule cells is dependent on incubation time ( t 1/2 of 2.6 ± 0.8 min at 37°C) and temperature. The accumulation of AEA is saturable and has an apparent K m of 41 ± 15 µ M and a V max of 0.61 ± 0.04 nmol/min/106 cells. [3 H]AEA accumulation by cerebellar granule cells is significantly reduced by 200 µ M phloretin (57.4 ± 4% of control) in a noncompetitive manner. [3 H]AEA accumulation is not inhibited by either ouabain or removal of extracellular sodium. [3 H]AEA accumulation is fairly selective for AEA among other naturally occurring N -acylethanolamines; only N -oleoylethanolamine significantly inhibited [3 H]AEA accumulation at a concentration of 10 µ M . The ethanolamides of palmitic acid and linolenic acid were inactive at 10 µ M . N -Arachidonoylbenzylamine and N -arachidonoylpropylamine, but not arachidonic acid, 15-hydroxy-AEA, or 12-hydroxy-AEA, compete for AEA accumulation. When cells are preloaded with [3 H]AEA, temperature-dependent efflux occurs with a half-life of 1.9 ± 1.0 min. Phloretin does not inhibit [3 H]AEA efflux from cells. These results suggest that AEA is accumulated by cerebellar granule cells by a protein-mediated transport process that has the characteristics of facilitated diffusion. 相似文献
12.
Laura J. Sim-Selley Paulette B. Goforth Mba U. Mba Timothy L. Macdonald† Kevin R. Lynch‡ Sheldon Milstien§ Sarah Spiegel§ Leslie S. Satin Sandra P. Welch Dana E. Selley 《Journal of neurochemistry》2009,110(4):1191-1202
Sphingosine-1-phosphate (S1P) is a ubiquitous, lipophilic cellular mediator that acts in part by activation of G-protein-coupled receptor. Modulation of S1P signaling is an emerging pharmacotherapeutic target for immunomodulatory drugs. Although multiple S1P receptor types exist in the CNS, little is known about their function. Here, we report that S1P stimulated G-protein activity in the CNS, and results from [35 S]GTPγS autoradiography using the S1P1 -selective agonist SEW2871 and the S1P1/3 -selective antagonist VPC44116 show that in several regions a majority of this activity is mediated by S1P1 receptors. S1P receptor activation inhibited glutamatergic neurotransmission as determined by electrophysiological recordings in cortical neurons in vitro , and this effect was mimicked by SEW2871 and inhibited by VPC44116. Moreover, central administration of S1P produced in vivo effects resembling the actions of cannabinoids, including thermal antinociception, hypothermia, catalepsy and hypolocomotion, but these actions were independent of CB1 receptors. At least one of the central effects of S1P, thermal antinociception, is also at least partly S1P1 receptor mediated because it was produced by SEW2871 and attenuated by VPC44116. These results indicate that CNS S1P receptors are part of a physiologically relevant and widespread neuromodulatory system, and that the S1P1 receptor contributes to S1P-mediated antinociception. 相似文献
13.
Neurosteroids Modulate Nicotinic Receptor Function in Mouse Striatal and Thalamic Synaptosomes 总被引:4,自引:1,他引:3
Amy E. Bullock Amy L. Clark Sharon R. Grady Scott F. Robinson Brian S. Slobe Michael J. Marks Allan C. Collins 《Journal of neurochemistry》1997,68(6):2412-2423
Abstract: Progesterone and its A-ring reduced metabolites are allosteric activators of GABAA receptors. The studies reported here examined the effects of these steroids on brain nicotinic receptors using an 86 Rb+ efflux assay that likely measures the function of α4β2-type nicotinic receptors and [3 H]dopamine release, which may be modulated by an α3-containing nicotinic receptor. Both of the A-ring reduced metabolites of progesterone were noncompetitive inhibitors of both assays, whereas progesterone inhibited only the 86 Rb+ efflux assay. The 86 Rb+ efflux assay was slightly more sensitive than was the dopamine release assay to steroid inhibition. Inhibition developed slowly for both assays ( t 1/2 = 0.4 min) and was reversed even more slowly ( t 1/2 = 10–15 min). Steroid addition did not alter either the rate of association of [3 H]nicotine binding to brain membranes, nor was equilibrium binding changed. These findings argue that neurosteroids are allosteric inhibitors of brain nicotinic receptors. 相似文献
14.
Ana Rita Álvaro Joana Rosmaninho-Salgado António F. Ambrósio† Cláudia Cavadas‡ 《Journal of neurochemistry》2009,109(5):1508-1515
Neuropeptide Y (NPY) and NPY receptors are widely distributed in the CNS, including the retina, but the role of NPY in the retina is largely unknown. The aim of this study was to investigate whether NPY modulates intracellular calcium concentration ([Ca2+ ]i ) changes in retinal neurons and identify the NPY receptors involved. As NPY decreased the [Ca2+ ]i amplitudes evoked by 30 mM KCl in only 50% of neurons analyzed, we divided them in two populations: NPY-non-responsive neurons (Δ2/Δ1 ≥ 0.80) and NPY-responsive neurons (Δ2/Δ1 < 0.80), being the Δ2/Δ1 the ratio between the amplitude of [Ca2+ ]i increase evoked by the second (Δ2) and the first (Δ1) stimuli of KCl. The NPY Y1 /Y5 , Y4 , and Y5 receptor agonists (100 nM), but not the Y2 receptor agonist (300 nM), inhibited the [Ca2+ ]i increase induced by KCl. In addition, the inhibitory effect of NPY on evoked-[Ca2+ ]i changes was reduced in the presence of the Y1 or the Y5 receptor antagonists. In conclusion, NPY inhibits KCl-evoked [Ca2+ ]i increase in retinal neurons through the activation of NPY Y1 , Y4 , and Y5 receptors. This effect may be viewed as a potential neuroprotective mechanism of NPY against retinal neurodegeneration. 相似文献
15.
The Desglycinyl Metabolite of Remacemide Hydrochloride Is Neuroprotective in Cultured Rat Cortical Neurons 总被引:1,自引:0,他引:1
Marsha A. Black Roger Tremblay Geoffrey A. R. Mealing Jon P. Durkin James F. Whitfield Paul Morley 《Journal of neurochemistry》1996,66(3):989-995
Abstract: The neuroprotective actions of remacemide and its anticonvulsant metabolite 1,2-diphenyl-2-propylamine monohydrochloride (desglycinylremacemide; DGR), a low-affinity NMDA receptor antagonist, were investigated using primary rat cortical neuronal cultures. Exposure of cortical cultures to NMDA (100 µ M ) for 15 min killed 85% of the neurons during the next 24 h. This neurotoxicity was blocked in a concentration-dependent manner by adding DGR (5–20 µ M ), but not its remacemide precursor (10–100 µ M ), to the cultures during the time of NMDA exposure. This suggests that the neuroprotective, as well as the anticonvulsant, activity of remacemide is mediated by DGR. Neuroprotective concentrations of DGR also inhibited two of the principal acute effects of NMDA. DGR (5–20 µ M ) prevented the loss of membrane-associated protein kinase C (PKC) activity that developed by 4 h after transient exposure to 100 µ M NMDA and reduced the NMDA-triggered increases in intracellular free Ca2+ concentration ([Ca2+ ]i ) by up to 70%. By contrast, remacemide (50 and 100 µ M ) did not prevent the NMDA-induced loss of PKC activity or reduce the [Ca2+ ]i responses. These data suggest that DGR protection against NMDA-mediated toxicity in cultured cortical neurons is associated with a reduction of NMDA-triggered [Ca2+ ]i surges and a prevention of the loss of membrane-associated PKC activity. In addition, the inhibition of NMDA-triggered [Ca2+ ]i responses by DGR was qualitatively different from the inhibition of these responses by the high-affinity NMDA-receptor antagonists MK-801 and phencyclidine. This may be a consequence of DGR's lower affinity for the NMDA receptor. 相似文献
16.
Hennigs JK Burhenne N Stähler F Winnig M Walter B Meyerhof W Schmale H 《Journal of neurochemistry》2008,106(5):2249-2262
In a search for sweet taste receptor interacting proteins, we have identified the calcium- and integrin-binding protein 1 (CIB1) as specific binding partner of the intracellular carboxyterminal domain of the rat sweet taste receptor subunit Tas1r2. In heterologous human embryonic kidney 293 (HEK293) cells, the G protein chimeras Gα16gust44 and Gα15i3 link the sweet taste receptor dimer TAS1R2/TAS1R3 to an inositol 1,4,5-trisphosphate (InsP3 )-dependent Ca2+ release pathway. To demonstrate the influence of CIB1 on the cytosolic Ca2+ concentration, we used sweet and umami compounds as well as other InsP3 -generating ligands in FURA-2-based Ca2+ assays in wild-type HEK293 cells and HEK293 cells expressing functional human sweet and umami taste receptor dimers. Stable and transient depletion of CIB1 by short-hairpin RNA increased the Ca2+ response of HEK293 cells to the InsP3 -generating ligands ATP, UTP and carbachol. Over-expression of CIB1 had the opposite effect as shown for the sweet ligand saccharin, the umami receptor ligand monosodium glutamate and UTP. The CIB1 effect was dependent on the thapsigargin-sensitive Ca2+ store of the endoplasmic reticulum (ER) and independent of extracellular Ca2+ . The function of CIB1 on InsP3 -evoked Ca2+ release from the ER is most likely mediated by its interaction with the InsP3 receptor. Thus, CIB1 seems to be an inhibitor of InsP3 -dependent Ca2+ release in vivo . 相似文献
17.
Nadine Aubin Olivier Curet Annie Deffois Chris Carter 《Journal of neurochemistry》1998,71(4):1635-1642
18.
Tachykinins Potentiate N-Methyl-D-Aspartate Responses in Acutely Isolated Neurons from the Dorsal Horn 总被引:6,自引:0,他引:6
K. I. Rusin D. Bleakman P. S. Chard M. Randic R. J. Miller 《Journal of neurochemistry》1993,60(3):952-960
Abstract: Substance P and neurokinin A both potentiated N -methyl- d -aspartate (NMDA)-induced currents recorded in acutely isolated neurons from the dorsal horn of the rat. To elucidate the mechanism underlying this phenomenon, we measured the effects of tachykinins and glutamate receptor agonists on [Ca2+ ]i in these cells. Substance P, but not neurokinin A, increased [Ca2+ ]i in a subpopulation of neurons. The increase in [Ca2+ ]i was found to be due to Ca2+ influx through voltage-sensitive Ca2+ channels. Substance P and neurokinin A also potentiated the increase in [Ca2+ ]i produced by NMDA, but not by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, or 50 m M K+ . Phorbol esters enhanced the effects of NMDA and staurosporine inhibited the potentiation of NMDA effects by tachykinins. It is concluded that activation of protein kinase C may mediate the enhancement of NMDA effects by tachykinins in these cells. However, the effects of tachykinins on [Ca2+ ]i can be dissociated from their effects on NMDA receptors. 相似文献
19.
Abstract: Cross talk between two phospholipase C (PLC)-linked receptor signalings was investigated in SK-N-BE(2)C human neuroblastoma cells. Sequential stimulation with two agonists at 5-min intervals was performed to examine the interaction between muscarinic and bradykinin (BK) receptors. Pretreatment of cells with a maximal effective concentration (5 µ M ) of BK did not affect the subsequent carbachol (CCh)-induced [Ca2+ ]i rise, but CCh (1 m M ) pretreatment completely abolished the BK-induced [Ca2+ ]i rise without inhibition of BK-induced inositol 1,4,5-trisphosphate (IP3 ) generation. Thapsigargin (1 µ M ) pretreatment abolished the subsequent BK- and CCh-induced [Ca2+ ]i rise, though it did not affect agonist-induced IP3 generation. However, the addition of atropine at plateau phases of CCh-induced [Ca2+ ]i rise and IP3 production caused a rapid decline to the basal levels and then restored the [Ca2+ ]i rise by BK. Treatment of cells with both CCh and BK at the same time showed additive effects in IP3 production. However, the [Ca2+ ]i rise induced by both agonists in the presence or absence of extracellular Ca2+ was the same as the responses triggered by CCh alone. The results suggest that each receptor or receptor-linked PLC activity is not influenced by pretreatment with the other agonist but IP3 -sensitive Ca2+ stores are shared by signal pathways from both receptors. 相似文献
20.
During hypoxia, extracellular adenosine levels are increased to prevent cell damage, playing a neuroprotective role mainly through adenosine A1 receptors. The aim of the present study was to analyze the effect of hypoxia in both adenosine A1 and A2A receptors endogenously expressed in C6 glioma cells. Two hours of hypoxia (5% O2 ) caused a significant decrease in adenosine A1 receptors. The same effect was observed at 6 h and 24 h of hypoxia. However, adenosine A2A receptors were significantly increased at the same times. These effects were not due to hypoxia-induced alterations in cells number or viability. Changes in receptor density were not associated with variations in the rate of gene expression. Furthermore, hypoxia did not alter HIF-1α expression in C6 cells. However, HIF-3α, CREB and CREM were decreased. Adenosine A1 and A2A receptor density in normoxic C6 cells treated with adenosine for 2, 6 and 24 h was similar to that observed in cells after oxygen deprivation. When C6 cells were subjected to hypoxia in the presence of adenosine deaminase, the density of receptors was not significantly modulated. Moreover, DPCPX, an A1 receptor antagonist, blocked the effects of hypoxia on these receptors, while ZM241385, an A2A receptor antagonist, was unable to prevent these changes. These results suggest that moderate hypoxia modulates adenosine receptors and cAMP response elements in glial cells, through a mechanism in which endogenous adenosine and tonic A1 receptor activation is involved. 相似文献