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NEUROPHARMACOLOGY
Mental Health Research Institute (A.M.H., D.K., G.T.G., A.T.V., S.K.F.) and Department of Pharmacology (S.K.F.), University of Michigan, Ann Arbor, Michigan
Received June 10, 2004; accepted July 30, 2004.
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Abstract |
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-cyano-(3,4-dihydroxy)cinnamonitrile. The results indicate that the activation of M3 mAChRs on SH-SY5Y neuroblastoma facilitates the ability of these cells to respond to very limited reductions in osmolarity via a release of osmolytes. mAChR-stimulated osmolyte efflux is mediated via a VSOAC and seems to require the activity of a tyrosine kinase.
). To counter these deleterious changes, neural cells initially restore their osmotic balance via a loss of K+ and Cl- ions. However, because large changes in ion concentrations can adversely impact excitability, cells subsequently use "compatible" or nonperturbing organic osmolytes to counter changes in osmolarity without compromising cell function. In the CNS, the three quantitatively major organic osmolytes are taurine, glutamate, and myo-inositol. Organic osmolytes are released from neural cells via a volume-sensitive organic anion channel (VSOAC), a channel that has been extensively characterized both electrophysiologically and pharmacologically, although its molecular structure remains unknown. VSOAC is selective for anions (primarily Cl-) and organic osmolytes, but it is impermeant to cations (for reviews, see Nilius et al., 1997; Lang et al., 1998; Nilius and Droogmans, 2003). The efflux of these osmolytes, along with the attendant loss of water from cells, restores the osmotic balance of the cell via a "regulatory volume decrease" (McManus et al., 1995; Pasantes-Morales et al., 2002).
Relatively little is known of the cell signaling pathways required for swelling-induced opening of VSOAC and osmolyte efflux, with the exception that a tyrosine kinase has been implicated in several, but not all, cell types (Mongin and Orlov, 2001; Jakab et al., 2002). Furthermore, although there is some evidence from non-neural preparations that VSOAC activation can be regulated by extracellular agonists (Tsumura et al., 1996; Manopoulos et al., 1997; Du and Sorota, 2000), the question of whether VSOAC activity in neural cells is also under neurohumoral control, and if so, the identities of the receptor subtypes involved, has largely remained unexplored. This issue is of particular importance to the CNS where cells exposed to hypotonic stress in vivo are also likely to be continuously subjected to released neurotransmitters.
In a recent study, we observed that activation of muscarinic cholinergic receptors (mAChRs) present on human SH-SY5Y neuroblastoma cells resulted in an enhancement of the volume-sensitive efflux of myo-inositol, a process mediated in part by an increased Ca2+ influx and protein kinase C activation (Loveday et al., 2003). However, because of the molecular dimensions of inositol (7.2 x 5.9 Å) in relation to the diameter of VSOAC (approximately 5-8 Å; McManus et al., 1995; Nilius et al., 1997), relatively large reductions in osmolarity were required for the detection of both basal- (no agonist) and agonist-stimulated efflux of the polyol. We have now extended these initial findings in SH-SY5Y cells by examining the efflux of two additional osmolytes, namely, taurine and D-aspartate (as a marker for glutamate efflux), which, due to their molecular dimensions, are more readily released by hypoosmotically stressed cells than myo-inositol. The monitoring of both these osmolytes addresses the possibility of the existence of distinct VSOACs specific for each osmolyte and potentially exhibiting different properties (Mongin et al., 1999; Franco et al., 2001; Ochoa de la Paz et al., 2002). The specific objectives of the present study were to 1) monitor taurine and D-aspartate release from SH-SY5Y cells under conditions of relatively limited alterations in osmolarity (such as those that might be encountered in vivo), in the absence and presence of mAChR activation; 2) pharmacologically identify the mAChR subtype coupled to enhanced osmolyte efflux; 3) determine whether the VSOAC mediates both the basal- and agonist-mediated efflux of taurine and D-aspartate; and 4) determine the role, if any, played by tyrosine kinase activity in agonist-stimulated osmolyte release.
The results indicate that the activation of M3 mAChRs on SH-SY5Y neuroblastoma markedly facilitates the cell's ability to release both taurine and D-aspartate. Not only does mAChR activation enhance osmolyte release over a wide range of osmolarities but also it lowers the threshold osmolarity at which the efflux of taurine and D-aspartate can occur. The agonist-stimulated efflux of osmolytes was inhibited by anion channel blockers, indicating the involvement of VSOAC, and was also dependent upon tyrosine kinase activity.
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Cell Culture Conditions. SH-SY5Y cells (passages 69-93) were grown in tissue culture flasks (75 cm2/250 ml) in 20 ml of DMEM supplemented with 10% (v/v) of fetal calf serum. The osmolarity of the medium was 330 to 340 mOsM. Cells were grown for 3 to 10 days at 37°C in a humidified atmosphere containing 10% CO2. Cells were isolated after aspiration of the medium and incubation with a modified Puck's D1 solution (Honneger and Richelson, 1976). Cells were then resuspended in DMEM/10% fetal calf serum and subcultured into 35-mm, six-well culture plates for 2 to 4 days. Experiments were routinely conducted on cells that had reached 50 to 90% confluence. Results obtained were independent of the passage number and confluence of cells.
Efflux of Taurine and D-Aspartate. Osmolyte efflux from SH-SY5Y neuroblastoma cells was monitored essentially as described previously (Loveday et al., 2003), with the exception that a double labeling (3H/14C) paradigm was employed. Cells grown in six-well plates were first allowed to prelabel at 37°C for 24 to 48 h in the presence of 100 KBq/ml D-[3H]aspartate and for an additional 3 to 24 h in the presence of 10 KBq/ml [14C]taurine. After prelabeling, the medium was aspirated, and cells were washed with 2 x 2 ml of isotonic buffer A (142 mM NaCl, 5.6 mM KCl, 2.2 mM CaCl2, 3.6 mM NaHCO3, 1 mM MgCl2, and 30 mM HEPES, pH 7.4). Cells were then allowed to incubate in 2 ml of either isotonic buffer A (approx. 340 mOsM) or hypotonic buffer A (160-320 mOsM; rendered hypotonic by the reduction in NaCl concentration). In some experiments, buffer A was made hypertonic (380 mOsM) by the addition of NaCl. Osmolarities of buffer A were monitored by means of an Osmette precision osmometer (PS Precision Systems, Sudbury, MA). At the times indicated, 200-µl aliquots of the extracellular medium were removed, and radioactivity was determined after the addition of 5 ml of Universol scintillation fluid. Radioactivity was monitored in a Packard 2250 CA liquid scintillation counter using a dual label program for 3H/14C. Spillover of radioactivity from 14C to 3H channel was <5%, whereas <0.5% of 3H radioactivity was recovered in the 14C channel.
To terminate the reactions, the medium was rapidly aspirated, the cells were lysed with 2 x 1 ml of ice-cold 6% (w/v) trichloroacetic acid, and water-soluble radioactivity was determined as described previously (Novak et al., 1999). Total water-soluble radioactivity present initially in the cells was calculated as the sum of that recovered in the extracellular medium and that remaining in the lysate at the end of the assay. Efflux of either D-aspartate or taurine at any given time was then routinely expressed as the ratio of radioactivity present in the extracellular medium to total soluble radioactivity (as a percentage), as detailed previously (Novak et al., 1999).
Phosphoinositide Turnover. To monitor phosphoinositide turnover, SH-SY5Y cells that had been prelabeled with 148 KBq/ml [3H]inositol for 48 h were incubated in hypotonic buffer A (230 mOsM) that contained 5 mM LiCl. The accumulation of radiolabeled inositol phosphates present in the trichloroacetic acid cell lysates was determined as described previously (Thompson and Fisher, 1990).
Data Analysis. Values quoted are means ± S.E.M. for the numbers of independent experiments indicated. Statistical significance of the differences between multiple groups was tested using a one-way analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. A two-tailed Student's t test (paired or unpaired) was used to evaluate the differences between two experimental groups. Values that were associated with a probability (p value) of <0.05 were considered to be significant. EC50 and IC50 values, 95% confidence intervals, and Hill slope factors were obtained using Prism 4.0 (GraphPad Software, Inc., San Diego, CA). IC50 values were converted to Ki values (assuming simple competition) by means of the Cheng and Prusoff (1973) equation.
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Dose Dependence and Pharmacological Characterization of Oxo-M-Stimulated Release of Taurine and D-Aspartate. The addition of Oxo-M resulted in a dose-dependent stimulation of both taurine and D-aspartate release, with the threshold occurring at approx. 10 nM agonist and a maximum effect observed at 100 µM or 1 mM concentrations. EC50 values of 2.2 and 2.0 µM were obtained for taurine and D-aspartate efflux, respectively (Fig. 4). To investigate the identity of the mAChR subtype(s) coupled to osmolyte efflux, the ability of three muscarinic antagonists, namely, 4-DAMP (an inhibitor of M1/M3 mAChRs), pirenzepine (an inhibitor of M1/M4 mAChRs) and AF-DX 116 (an inhibitor of M2 mAChRs), to inhibit stimulated taurine and D-aspartate efflux was monitored (Fig. 5, A and B). The addition of all three agents resulted in a >90% inhibition of stimulated osmolyte efflux, but with markedly different affinities. The most potent inhibitor was 4-DAMP, whereas pirenzepine and AF-DX 116 were 100- to 1000-fold less potent, respectively. Apparent Ki values for stimulated taurine release, calculated from the Cheng and Prusoff equation, were 1.23 nM, 148 nM, and 1.16 µM for 4-DAMP, pirenzepine and AF-DX 116, respectively. The corresponding values for stimulated aspartate release were 1.14 nM, 156 nM, and 1.04 µM. A pharmacological profile similar to that obtained for taurine and D-aspartate release was also observed for Oxo-M-stimulated inositol phosphate release in that the rank order of potency for inhibition was 4-DAMP > pirenzepine > AF-DX 116. The apparent Ki values for inhibition of Oxo-M-stimulated inositol phosphate release for 4-DAMP, pirenzepine, and AF-DX 116 were 1.06 nM, 240 nM, and 1.90 µM, respectively (Fig. 5C).
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Anion Channel Blockers Inhibit Both Basal- and Oxo-M-Stimulated Osmolyte Release. The ability of five anion channel inhibitors, putative blockers of the VSOAC channel, to inhibit the basal efflux of taurine and D-aspartate was examined. Although inclusion of all five agents resulted in a significant inhibition of the basal release of taurine, dideoxyforskolin and NPPB (65-81% inhibition) were more effective than DIDS, SITS, or niflumic acid (35-55% inhibition; Fig. 6). The inhibitor profile for D-aspartate release was similar to that observed for taurine, with the exception that the stilbene-derivatives DIDS and SITS were significantly less effective as inhibitors of aspartate release. Thus, whereas inclusion of 100 µM DIDS resulted in a 50 ± 4% inhibition of taurine release, the corresponding value for aspartate release was 28 ± 3% (p < 0.0001). Similarly, SITS was a more effective inhibitor of taurine release than of aspartate release (p < 0.004). Although dideoxyforskolin was also a more effective inhibitor of taurine release than of aspartate efflux, this differential effect was less marked than for either DIDS or SITS. In a separate series of experiments, the ability of VSOAC inhibitors to inhibit the agonist-stimulated component of osmolyte release was examined. However, because of the possible complication that these agents might also (nonspecifically) directly interfere with mAChR signaling, we first determined the effect of VSOAC inhibitors on Oxo-M-stimulated inositol phosphate release. With the exception of NPPB (74 ± 3% of agonist alone; n = 3), none of the agents tested resulted in a significant inhibition of Oxo-M-stimulated inositol phosphate release. The two agents chosen for further evaluation of osmolyte efflux were DIDS (because of its widespread prior use) and dideoxyforskolin (because of its pronounced ability to inhibit VSOAC; Fig. 6). As observed previously, inclusion of 200 µM DIDS more effectively inhibited the basal release of taurine than that of D-aspartate. However DIDS also resulted in a significant reduction in the magnitude of osmolyte release observed in the presence of Oxo-M, by an extent greater than that attributable to the inhibition of basal release (Fig. 7A). Although DIDS inhibited the Oxo-M-mediated stimulation of both osmolytes, taurine efflux was inhibited to a greater extent (34 ± 3 versus 23 ± 2% for aspartate efflux; p < 0.015). Inclusion of 100 µM dideoxyforskolin resulted in a more pronounced inhibition of both basal- and Oxo-M-stimulated taurine/D-aspartate release, with Oxo-M stimulation of taurine release (90 ± 1%) being marginally more inhibited than that of aspartate release (86 ± 1%; p < 0.03) (Fig. 7B).
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Modulation of Basal- and mAChR-Stimulated Osmolyte Release by Inhibitors of Tyrosine Kinases and Tyrosine Phosphatases. Inclusion of 50 or 100 µM concentrations of the tyrosine kinase inhibitor AG-18 inhibited the basal release of both taurine and D-aspartate by 31 to 32% (Fig. 8A). In contrast, the inactive analog AG-9 (100 µM) was without effect on basal osmolyte release (Fig. 8B). AG-18 also resulted in a 61 to 69% inhibition of Oxo-M-stimulated taurine and D-aspartate release, whereas AG-9 had no effect. Part, at least, of the ability of AG-18 to inhibit stimulated osmolyte release may be attributable to an inhibitory effect of the tyrphostin on Oxo-M-stimulated inositol phosphate release (22 ± 5% inhibition; n = 5). Other known inhibitors of tyrosine kinases, such as genistein (100 µM) or AG-112 (100 µM) had little or no effect on either basal- or Oxo-M-stimulated osmolyte release. Although inclusion of herbimycin (1 µM) also had no significant effect on basal osmolyte release, it inhibited Oxo-M-stimulated release of taurine and aspartate by 25 and 18%, respectively (n = 5; p < 0.04). Inclusion of 100 µM orthovanadate or 10 µM mpV, inhibitors of tyrosine phosphatases, resulted in an increase in the basal release of taurine and aspartate of approximately 40 to 80% (Fig. 9). The presence of orthovanadate (but not mpV) also resulted in a marked (40%; p = 0.003) synergistic increase in osmolyte release, when monitored in the presence of the agonist. This ability of orthovanadate to potentiate osmolyte release was accompanied by an enhancement of mAChR-stimulated inositol phosphate release (24% increase; p < 0.03; Fig. 9). Inhibitors of other kinases, such as wortmannin (100 nM; phosphatidylinositol 3-kinase) or PD 98059 (50 µM; mitogen-activated protein kinase), had no effect on either the basal- or Oxo-M-stimulated release of taurine or D-aspartate (data not shown).
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), who observed that activation of purinergic receptors markedly increased the release of D-aspartate from astrocytes under conditions of mild hypotonicity (10% reduction from isotonic), conditions under which the basal release of the osmolyte was only minimally increased. In addition, similar to our current findings in neuroblastoma, receptor activation of D-aspartate release from astrocytes was observed under isotonic conditions. Taken collectively, these data suggest that the neurohumoral regulation of VSOAC may enable a neural cell to more efficiently release its osmolytes when placed under hypotonic stress.
Although immunoprecipitation data from this and other laboratories suggest that mAChRs present on SH-SY5Y cells are predominantly (70-80%) of the m3 subtype, m1, m2, and m4 mAChRs are also found (Wall et al., 1991; Sloweijko et al., 1994). To determine which of these mAChR subtypes mediated the increased osmolyte efflux, studies were conducted with three muscarinic antagonists, namely, 4-DAMP, pirenzepine, and AF DX-116, each of which exhibits very different binding affinities for these subtypes (Fisher and Heacock, 1988; Lambert et al., 1989; Caulfield and Birdsall, 1998). The results demonstrate that it is the activation of the M3 receptors that leads to an enhancement of the efflux of taurine and D-aspartate. The pharmacological inhibition profile of efflux, i.e., 4-DAMP > pirenzepine > AF DX-116 is identical to that obtained for stimulated phosphoinositide hydrolysis (Fig. 5C), which is also mediated by the M3 mAChR. In addition, the Ki values obtained for inhibition of stimulated efflux and inositol lipid hydrolysis in the presence of 4-DAMP, pirenzepine, and AF DX-116 are also very similar to their binding affinities obtained from radioligand binding studies (Lambert et al., 1989). To the best of our knowledge, this is the first identification of a specific receptor subtype that is coupled to osmolyte efflux. The fact that agonist occupancy of M3 mAChRs results in both a stimulation of osmolyte release and an increase in phosphoinositide hydrolysis raises the possibility that these two sequelae of receptor activation may be functionally linked. In our previous study, we demonstrated that the mAChR-stimulated efflux of myo-inositol was dependent upon Ca2+ influx and protein kinase C, results that are consistent with an involvement of phosphoinositide hydrolysis in osmolyte efflux (Loveday et al., 2003). However, because mAChR activation in SH-SY5Y cells can result in a number of additional biochemical consequences, e.g., activation of small-molecular-weight GTP-binding proteins and nonreceptor tyrosine kinases (Linseman et al., 2000, 2001), the possibility remains that activation of more than one pathway is required for osmolyte efflux. Thus, an obligatory link between the activation of phospholipase C and the enhancement of osmolyte efflux, although feasible, remains to be established.
Evidence that VSOAC mediates both basal- and agonist-stimulated efflux of taurine and D-aspartate was obtained from experiments in which the inclusion of anion channel blockers inhibited both responses. Taurine release from SH-SY5Y cells was found to be more sensitive than that of aspartate release to some anion channel blockers. Although there was a tendency for all of the VSOAC inhibitors to preferentially inhibit taurine release, this effect was most marked for the stilbene derivatives DIDS and SITS (Fig. 6). This differential ability of DIDS and SITS to preferentially block taurine release has previously been observed for other neural preparations and has led to the speculation that more than one VSOAC channel may mediate osmolyte efflux (Rutledge et al., 1998; Franco et al., 2001; Ochoa de la Paz et al., 2002). Although this remains a possibility for osmolyte efflux from SH-SY5Y cells, further evidence to support the concept of multiple VSOACs, e.g., from 1) differences in the rate of activation and deactivation of the release of individual osmolytes (Franco et al., 2001) and 2) differential inhibition of osmolyte release by tyrosine kinase inhibitors (Mongin et al., 1999; Franco et al., 2001; Ochoa de la Paz et al., 2002) was not obtained in the present study. Thus, although our data do not exclude the possible involvement of multiple VSOACs, the most parsimonious interpretation is that under both basal- and agonist-stimulated conditions, the efflux of taurine and D-aspartate from SH-SY5Y cells occurs predominantly via the same (or very similar) VSOAC channel(s).
Of the signaling pathways that have been implicated in the activation of osmolyte efflux after hypotonic stress, the involvement of a tyrosine kinase activity has been widely reported in many, but not all, cells (Jakab et al., 2002). Our data, which demonstrate the inhibition of taurine and D-aspartate release (both basal- and agonist-stimulated) by the active tyrphostin AG-18 but not by the inactive analog AG-9 would also support the possibility that a tyrosine kinase is required for VSOAC activation in SH-SY5Y cells. Other tyrosine kinase inhibitors, e.g., genistein, AG-112, and herbimycin, had much less or no effect on osmolyte efflux. Large differences in the efficacy with which these tyrosine kinase inhibitors block osmolyte release have previously been reported for other neural tissue preparations (Crépel et al., 1998; Franco et al., 2001; Ochoa de la Paz et al., 2002). In contrast to the results obtained in some previous studies in which tyrphostins preferentially inhibited taurine release (Mongin et al., 1999; Franco et al., 2001; Ochoa de la Paz et al., 2002), AG-18 was equally effective in the inhibition of taurine and D-aspartate efflux from SH-SY5Y cells. Further evidence to implicate a tyrosine kinase in osmolyte efflux was obtained from studies of the effects of orthovanadate and mpV, both of which can act as inhibitors of tyrosine phosphatases (Posner et al., 1994). Orthovanadate, but not mpV, also potentiated the agonist-stimulated efflux of taurine and D-aspartate, a response that seems to be related to its ability, via an as yet unknown mechanism, to enhance Oxo-M- (but not basal)-stimulated phosphoinositide hydrolysis.
In summary, the present data indicate that the activation of M3 mAChRs on SH-SY5Y cells facilitates the ability of cells to release osmolytes under conditions of limited reductions in osmolarity. The enhanced osmolyte release is mediated via a VSOAC channel and seems to require the involvement of a tyrosine kinase. The ability of neurotransmitters, acting via pharmacologically specific receptor subtypes, to increase osmolyte release raises the possibility that this mechanism could provide a means whereby neural cells are able to more readily restore their volume in response to hypotonic stress.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
ABBREVIATIONS: CNS, central nervous system; VSOAC, volume-sensitive organic anion channel; mAChR, muscarinic cholinergic receptor; DIDS, 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid; Oxo-M, oxotremorine-M; NPPB, 5-nitro-2-(3-phenylpropylamino) benzoic acid; 4-DAMP, 4-diphenylacetoxy-N-methylpiperidine methiodide; SITS, 4-acetamido-4'-isothiocyanatostilbene 2,2'-disulfonic acid; AG-9, -cyano-(4-methoxyl)cinnamonitrile; AG-18, -cyano-(3,4-dihydroxy)cinnamonitrile; AG-112, 2-amino-4-(4'-hydroxyphenyl)-1,1,3-tricyanobuta-1,3-diene; mpV, monoperoxo vanadium (picolinato); PD 98059, 2'-amino-3'-methoxyflavone; AF-DX 116, 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one; DMEM, Dulbecco's modified Eagle's medium; ANOVA, analysis of variance.
Address correspondence to: Dr. Stephen K. Fisher, Mental Health Research Institute Laboratories at MSRB II, 1150 West Medical Center Dr., C560, MSRB II, University of Michigan, Ann Arbor, MI 48109-0669. E-mail: skfisher{at}umich.edu
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References |
|---|
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TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Caulfield MP and Birdsall NJ (1998) International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 50: 279-290.
Cheng Y and Prusoff WH (1973) Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22: 3099-3108.[CrossRef][Medline]
Crépel V, Panenka W, Kelly ME, and MacVicar BA (1998) Mitogen-activated protein and tyrosine kinases in the activation of astrocyte volume-activated chloride current. J Neurosci 18: 1196-1206.
Du XY and Sorota S (2000) Cardiac swelling-induced chloride current is enhanced by endothelin. J Cardiovasc Pharmacol 35: 769-776.[CrossRef][Medline]
Fisher SK and Heacock AM (1988) A putative M3 muscarinic cholinergic receptor of high molecular weight couples to phosphoinositide hydrolysis in human SK-N-SH neuroblastoma cells. J Neurochem 50: 984-987.[CrossRef][Medline]
Franco R, Torres-Marquez ME, and Pasantes-Morales H (2001) Evidence for two mechanisms of amino acid osmolyte release from hippocampal slices. Pflueg Arch 442: 791-800.[CrossRef][Medline]
Honegger P and Richelson E (1976) Biochemical differentiation of mechanically dissociated mammalian brain in aggregating cell culture. Brain Res 109: 335-354.[CrossRef][Medline]
Jakab M, Furst J, Gschwentner M, Botta G, Garavaglia ML, Bazzini C, Rodighiero S, Meyer G, Eichmueller S, Woll E, et al. (2002) Mechanisms sensing and modulating signals arising from cell swelling. Cell Physiol Biochem 12: 235-258.[CrossRef][Medline]
Lambert DG, Ghataorre AS, and Nahorski SR (1989) Muscarinic receptor binding characteristics of a human neuroblastoma SK-N-SH and its clones SH-SY5Y and SH-EP1. Eur J Pharmacol 165: 71-77.[CrossRef][Medline]
Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, and Haussinger D (1998) Functional significance of cell volume regulatory mechanisms. Physiol Rev 78: 247-306.
Linseman DA, Heidenreich KA, and Fisher SK (2001) Stimulation of M3 muscarinic receptors induces phosphorylation of the Cdc42 effector activated Cdc42Hs-associated kinase-1 via a Fyn tyrosine kinase signaling pathway. J Biol Chem 276: 5622-5628.
Linseman DA, Hofmann F, and Fisher SK (2000) A role for the small molecular weight GTPases, Rho and Cdc42, in muscarinic receptor signaling to focal adhesion kinase. J Neurochem 74: 2010-2020.[CrossRef][Medline]
Loveday D, Heacock AM, and Fisher SK (2003) Activation of muscarinic cholinergic receptors enhances the volume-sensitive efflux of myo-inositol from SH-SY5Y neuroblastoma cells. J Neurochem 87: 476-486.[CrossRef][Medline]
Manolopoulos GV, Prenen J, Droogmans G, and Nilius B (1997) Thrombin potentiates volume-activated chloride currents in pulmonary artery endothelial cells. Pflueg Arch 433: 845-847.[CrossRef][Medline]
McManus ML, Churchwell KB, and Strange K (1995) Regulation of cell volume in health and disease. N Engl J Med 333: 1260-1266.
Mongin AA and Kimelberg HK (2002) ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes. Am J Physiol 283: C569-C578.
Mongin AA and Orlov SN (2001) Mechanisms of cell volume regulation and possible nature of the cell volume sensor. Pathophysiology 8: 77-88.[CrossRef][Medline]
Mongin AA, Reddi JM, Charniga C, and Kimelberg HK (1999) [3H]taurine and D-[3H]aspartate release from astrocyte cultures are differently regulated by tyrosine kinases. Am J Physiol 276: C1226-C1230.
Nilius B and Droogmans G (2003) Amazing chloride channels: an overview. Acta Physiol Scand 177: 119-147.[CrossRef][Medline]
Nilius B, Eggermont J, Voets T, Buyse G, Manolopoulos V, and Droogmans G (1997) Properties of volume-regulated anion channels in mammalian cells. Prog Biophys Mol Biol 68: 69-119.[CrossRef][Medline]
Novak JE, Turner RS, Agranoff BW, and Fisher SK (1999) Differentiated human NT2-N neurons possess a high intracellular content of myo-inositol. J Neurochem 72: 1431-1440.[CrossRef][Medline]
Ochoa de la Paz LD, Lezama R, Torres-Marquez ME, and Pasantes-Morales H (2002) Tyrosine kinases and amino acid efflux under hyposmotic and ischaemic conditions in the chicken retina. Pflueg Arch 445: 87-96.[CrossRef][Medline]
Pasantes-Morales H, Cardin V, and Tuz K (2000) Signaling events during swelling and regulatory volume decrease. Neurochem Res 25: 1301-1314.[CrossRef][Medline]
Pasantes-Morales H, Franco R, Ordaz B, and Ochoa LD (2002) Mechanisms counteracting swelling in brain cells during hyponatremia. Arch Med Res 33: 237-244.[CrossRef][Medline]
Posner BI, Faure R, Burgess JW, Bevan AP, Lachance D, Zhang-Sun G, Fantus IG, Ng JB, Hall DA, Lum BS, et al. (1994) Peroxovanadium compounds. A new class of potent phosphotyrosine phosphatase inhibitors which are insulin mimetics. J Biol Chem 269: 4596-4604.
Rutledge EM, Aschner M, and Kimelberg HK (1998) Pharmacological characterization of swelling-induced D-[3H]aspartate release from primary astrocyte cultures. Am J Physiol 274: C1511-C1520.
Slowiejko DM, Levey AI, and Fisher SK (1994) Sequestration of muscarinic cholinergic receptors in permeabilized neuroblastoma cells. J Neurochem 62: 1795-1803.[Medline]
Thompson AK and Fisher SK (1990) Relationship between agonist-induced muscarinic receptor loss and desensitization of stimulated phosphoinositide turnover in two neuroblastomas: methodological considerations. J Pharmacol Exp Ther 252: 744-752.
Tsumura T, Oiki S, Ueda S, Okuma M, and Okada Y (1996) Sensitivity of volume-sensitive Cl- conductance in human epithelial cells to extracellular nucleotides. Am J Physiol 271: C1872-C1878.
Wall SJ, Yasuda RP, Li M, and Wolfe BB (1991) Development of an antiserum against m3 muscarinic receptors: distribution of m3 receptors in rat tissues and clonal cell lines. Mol Pharmacol 40: 783-789.[Abstract]
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A. M. Heacock, D. J. Foster, and S. K. Fisher Prostanoid Receptors Regulate the Volume-Sensitive Efflux of Osmolytes from Murine Fibroblasts via a Cyclic AMP-Dependent Mechanism J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 963 - 971. [Abstract] [Full Text] [PDF]
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A. M. Heacock, M. S. Dodd, and S. K. Fisher Regulation of Volume-Sensitive Osmolyte Efflux from Human SH-SY5Y Neuroblastoma Cells following Activation of Lysophospholipid Receptors J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 685 - 693. [Abstract] [Full Text] [PDF]
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T. A. Cheema, C. E. Ward, and S. K. Fisher Subnanomolar Concentrations of Thrombin Enhance the Volume-Sensitive Efflux of Taurine from Human 1321N1 Astrocytoma Cells J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 755 - 763. [Abstract] [Full Text] [PDF]
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