ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes

2002 ◽  
Vol 283 (2) ◽  
pp. C569-C578 ◽  
Author(s):  
Alexander A. Mongin ◽  
Harold K. Kimelberg
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Atp Release ◽  
Anion Channel ◽  
P2y Receptors ◽  
Cell Swelling ◽  
Channel Blockers ◽  
Medium Osmolarity ◽  
Subsequent Activation

Volume-dependent ATP release and subsequent activation of purinergic P2Y receptors have been implicated as an autocrine mechanism triggering activation of volume-regulated anion channels (VRACs) in hepatoma cells. In the brain ATP is released by both neurons and astrocytes and participates in intercellular communication. We explored whether ATP triggers or modulates the release of excitatory amino acid (EAAs) via VRACs in astrocytes in primary culture. Under basal conditions exogenous ATP (10 μM) activated a small EAA release in 70–80% of the cultures tested. In both moderately (5% reduction of medium osmolarity) and substantially (35% reduction of medium osmolarity) swollen astrocytes, exogenous ATP greatly potentiated EAA release. The effects of ATP were mimicked by P2Y agonists and eliminated by P2Y antagonists or the ATP scavenger apyrase. In contrast, the same pharmacological maneuvers did not inhibit volume-dependent EAA release in the absence of exogenous ATP, ruling out a requirement of autocrine ATP release for VRAC activation. The ATP effect in nonswollen and moderately swollen cells was eliminated by a 5–10% increase in medium osmolarity or by anion channel blockers but was insensitive to tetanus toxin pretreatment, further supporting VRAC involvement. Our data suggest that in astrocytes ATP does not trigger EAA release itself but acts synergistically with cell swelling. Moderate cell swelling and ATP may serve as two cooperative signals in bidirectional neuron-astrocyte communication in vivo.

Volume-associated osmolyte fluxes in cell lines with or without the anion exchanger

1995 ◽  
Vol 269 (5) ◽  
pp. C1280-C1286 ◽  
Author(s):  
R. Sanchez-Olea ◽  
C. Fuller ◽  
D. Benos ◽  
H. Pasantes-Morales
Keyword(s):  
Amino Acid ◽  
Cell Lines ◽  
Anion Exchanger ◽  
Chinese Hamster ◽  
Anion Channel ◽  
Cell Swelling ◽  
Disulfonic Acid ◽  
Channel Blockers ◽  
Cell Type ◽  
Amino Acid Efflux

To investigate the involvement of a red cell-type anion exchanger in the volume-sensitive amino acid release, the hyposmolarity-evoked release of D-[3H]aspartate and [3H]taurine was examined in three cell lines: 1) wild-type Chinese hamster ovary (CHO-K1) cells, expressing an anion exchanger activity (Cl-/SO4(2-)) functionally similar to the erythroid band 3; 2) a mutant CHO cell type (CHO 605) lacking this anion exchanger activity; and 3) 293 cells in which the Cl-/HCO3(-) anion exchanger is absent. All cell types accumulated D-[3H]aspartate and [3H]taurine under isosmotic conditions, and, similarly, in the three cell lines, cell swelling evoked by hyposmolarity induced a rapid and transient increase in the amino acid efflux. Blockers of the anion exchanger and/or Cl- channels [niflumic acid, dipyridamole, diphenylamine-2-carboxylate,5-nitro-2-(3-phenylpropylamino)-benzoi c acid, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid] were potent inhibitors of amino acid efflux in the three cell lines. 125I- efflux, used as a marker for Cl- fluxes, was also markedly increased in response to cell swelling in all cell lines, and this efflux was inhibited by the anion exchanger/Cl- channel blockers. These results do not support a role for an anion exchanger in the hyposmolarity-induced amino acid efflux and suggest that amino acids and Cl- may be transported by the same or a similar mechanism, presumably an anion channel-like structure.

Effect of bFGF on neuronal damage induced by sequential treatment of amyloid β and excitatory amino acid in vitro and in vivo

2012 ◽  
Vol 695 (1-3) ◽  
pp. 76-82 ◽  
Author(s):  
Takafumi Noshita ◽  
Norihito Murayama ◽  
Tetsushi Oka ◽  
Ryoko Ogino ◽  
Shizuo Nakamura ◽  
...  
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Neuronal Damage ◽  
Amyloid Β ◽  
Sequential Treatment

Anion channel blockers inhibit swelling-activated anion, cation, and nonelectrolyte transport in HeLa cells

1996 ◽  
Vol 271 (2) ◽  
pp. C579-C588 ◽  
Author(s):  
J. A. Hall ◽  
J. Kirk ◽  
J. R. Potts ◽  
C. Rae ◽  
K. Kirk
Keyword(s):  
Hela Cells ◽  
Anion Channel ◽  
Cell Swelling ◽  
Disulfonic Acid ◽  
Channel Blockers ◽  
Influx Rate ◽  
Cation Permeability ◽  
Transport Component ◽  
Selective Channel ◽  
Substrate Concentrations

The effect of osmotic cell swelling on the permeability of HeLa cells to a range of structurally unrelated solutes including taurine, sorbitol, thymidine, choline, and K+ (96Rb+) was investigated. For each solute tested, reduction in the osmolality of the medium from 300 to 200 mosmol/kgH2O caused a significant increase in the unidirectional influx rate. In each case, the osmotically activated transport component was nonsaturable up to external substrate concentrations of 50 mM. Inhibitors of the swelling-activated anion channel of HeLa cells [quinine, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, niflumate, 1,9-dideoxyforskolin, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), and tamoxifen] blocked the osmotically activated influx of each of the different substrates tested, as well as the osmotically activated efflux of taurine and I-. Tamoxifen and NPPB were similarly effective at blocking the osmotically activated efflux of 96Rb+. The simplest of several hypotheses consistent with the data is that the osmotically activated transport of the different solutes tested here is via a swelling-activated anion-selective channel that has a significant cation permeability and a minimum pore diameter of 8-9 A.

Mechanical strain-induced Ca2+waves are propagated via ATP release and purinergic receptor activation

2000 ◽  
Vol 279 (2) ◽  
pp. C295-C307 ◽  
Author(s):  
H. Sauer ◽  
J. Hescheler ◽  
M. Wartenberg
Keyword(s):  
Gap Junctions ◽  
Purinergic Receptor ◽  
Mechanical Strain ◽  
Atp Release ◽  
Anion Channel ◽  
Receptor Activation ◽  
Disulfonic Acid ◽  
Channel Blockers ◽  
Junctional Coupling ◽  
Intracellular Ca

Mechanical strain applied to prostate cancer cells induced an intracellular Ca2+ (Cai 2+) wave spreading with a velocity of 15 μm/s. Cai 2+ waves were not dependent on extracellular Ca2+ and membrane potential because propagation was unaffected in high-K+ and Ca2+-free solution. Waves did not depend on the cytoskeleton or gap junctions because cytochalasin B and nocodazole, which disrupt microfilaments and microtubules, respectively, and 1-heptanol, which uncouples gap junctions, were without effects. Fluorescence recovery after photobleaching experiments revealed an absence of gap junctional coupling. Cai 2+ waves were inhibited by the purinergic receptor antagonists basilen blue and suramin; by pretreatment with ATP, UTP, ADP, UDP, 2-methylthio-ATP, and benzoylbenzoyl-ATP; after depletion of ATP by 2-deoxyglucose; and after ATP scavenging by apyrase. Waves were abolished by the anion channel inhibitors 5-nitro-2-(3-phenylpropylamino)benzoic acid, tamoxifen, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, niflumic acid, and gadolinium. ATP release following strain was significantly inhibited by anion channel blockers. Hence, ATP is secreted via mechanosensitive anion channels and activates purinergic receptors on the same cell or neighboring cells in an autocrine and paracrine manner, thus leading to Cai 2+ wave propagation.

Ionotropic excitatory amino acid receptors in pre-Bötzinger complex play a modulatory role in hypoxia-induced gasping in vivo

2004 ◽  
Vol 96 (5) ◽  
pp. 1643-1650 ◽  
Author(s):  
Irene C. Solomon
Keyword(s):  
Amino Acid ◽  
Excitatory Amino Acid ◽  
Respiratory Rhythm ◽  
Receptor Activation ◽  
Induced Response ◽  
Brain Hypoxia ◽  
Bötzinger Complex ◽  
Before And After ◽  
Additional Support

Activation of ionotropic excitatory amino acid (EAA) receptors in pre-Bötzinger complex (pre-BötC) not only influences the eupneic pattern of phrenic motor output but also modifies hypoxia-induced gasping in vivo by increasing gasp frequency. Although ionotropic EAA receptor activation in this region appears to be required for the generation of eupneic breathing, it remains to be determined whether similar activation is necessary for the production and/or expression of hypoxia-induced gasping. Therefore, we examined the effects of severe brain hypoxia before and after blockade of ionotropic EAA receptors in the pre-BötC in eight chloralose-anesthetized, deafferented, mechanically ventilated cats. In each experiment, before blockade of ionotropic EAA receptors in the pre-BötC, severe brain hypoxia (6% O2 in a balance of N2 for 3-6 min) produced gasping. Although bilateral microinjection of the broad-spectrum ionotropic EAA receptor antagonist kynurenic acid (20-100 mM; 40 nl) into the pre-BötC eliminated basal phrenic nerve discharge, severe brain hypoxia still produced gasping. Under these conditions, however, the onset latency to gasping was increased ( P < 0.05), the number of gasps was reduced for the same duration of hypoxic gas exposure ( P < 0.05), the duration of gasps was prolonged ( P < 0.05), and the duration between gasps was increased ( P < 0.05). These findings demonstrate that hypoxia-induced gasping in vivo does not require activation of ionotropic EAA receptors in the pre-BötC, but ionotropic EAA receptor activation in this region may modify the expression of the hypoxia-induced response. The present findings also provide additional support for the pre-BötC as the primary locus of respiratory rhythm generation.

A novel multi-target ligand (JM-20) protects mitochondrial integrity, inhibits brain excitatory amino acid release and reduces cerebral ischemia injury in vitro and in vivo

2014 ◽  
Vol 85 ◽  
pp. 517-527 ◽  
Author(s):  
Yanier Nuñez-Figueredo ◽  
Jeney Ramírez-Sánchez ◽  
Gisele Hansel ◽  
Elisa Nicoloso Simões Pires ◽  
Nelson Merino ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cerebral Ischemia ◽  
Excitatory Amino Acid ◽  
Amino Acid Release ◽  
Mitochondrial Integrity ◽  
Acid Release
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