Ian Henry Lambert

• University of Copenhagen

The HDAC inhibitor trichostatine A (TSA) reduces cell viability in cisplatin-sensitive (A2780WT) and cisplatin-resistant (A2780RES) human ovarian cancer cells due to progression of apoptosis (increased caspase 9 activity), autophagy (increased LC3II expression) and cell cycle arrest (increased p21 expression). The TSA-mediated effect on p21 and cas...

The feasibility of quantitatively tracking platinum, derived from platinum-based compounds, during subcellular fractionation was studied. Cisplatin-exposed murine Ehrlich Lettré Ascites cells were fractionated into cytosolic and crude nuclear fractions. The latter was subsequently purified. Every residue and fraction produced during the fractionati...

Cisplatin is a widely used chemotherapeutic drug. Due to severe side effects and intrinsic or acquired resistance, there is a great interest in developing new platinum-based anticancer agents and a need for robust and validated analytical methods for determination of platinum accumulation in biological samples. A validated ICP-MS method for quantif...

The aim of this project was to gain insights into the uptake and cellular actions of the enantiomeric R- and S-1,1’-binaphthyl-2,2’-diaminodichlorido-Pt(II) complexes (R- and S-[Pt(DABN)Cl2]) in the cisplatin-sensitive human Burkitt lymphoma cell line (Gumbus, IC50: 1.3±0.2 µM) and its cisplatin-resistant sub-line (CDDPrGB IC50: 6.6±1.2 µM). The ce...

The leucine rich repeat containing 8A (LRRC8A) protein is an essential component of the volume sensitive organic anion channel (VSOAC) and using pharmacological anion channel inhibitors (NS3728, DIDS) and LRRC8A siRNA we have investigated its role in development of Cisplatin resistance in human ovarian (A2780) and alveolar (A549) carcinoma cells. I...

Volume-regulated channels for anions (VRAC) / organic osmolytes (VSOAC) play essential roles in cell volume regulation and other cellular functions, e.g. proliferation, cell migration and apoptosis. LRRC8A, which belongs to the leucine rich-repeat containing protein family, was recently shown to be an essential component of both VRAC and VSOAC. Red...

We have tested the effect of protolichesterinic acid (PA) on the activity of the volume-sensitive release pathway for the organic osmolyte taurine (VSOAC) and the expression of the leucine-rich-repeat-channel 8A (LRRC8A) protein, which constitutes an essential VSOAC component. Exposing human lung cancer cells (A549) to PA (20 µg/mL, 24 h) reduces L...

The aim of this project was to analyze the regulation of p53 expression in NIH3T3 fibroblasts under the influence of increasing hyperosmotic stress. Expression of p53 showed a biphasic response pattern in NIH3T3 cells under increasing osmotic stress (337 mOsm to 737 mOsm) with a maximum at 587 mOsm. Under isotonic conditions p53 expression increase...

Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β1, in cell volume regulation and drug-induced apoptosis in adherent and non-adher...

In the present work a novel C,N-cyclometalated benzimidazole Ru(ii) arene complex (GY34) was characterized by applying an alternative, diverse approach considering both chemical and biological aspects. RP-HPLC-ICP-MS and RP-HPLC-ESI-MS analysis proved that GY34 in both RPMI-1640 cell medium and ammonium acetate buffer was transformed into several s...

Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-) and H2O, respectively), were included as control sa...

Cisplatin resistance is a major challenge in the treatment of cancer and develops through reduced drug accumulation and an increased ability to avoid drug-induced cell damage, cell shrinkage and hence initiation of apoptosis. Uptake and release of the semi-essential amino acid taurine contribute to cell volume homeostasis and taurine has been repor...

Taurine is often referred to as a semi-essential amino acid as newborn mammals have a limited ability to synthesize taurine and have to rely on dietary supply. Taurine is not thought to be incorporated into proteins as no aminoacyl tRNA synthetase has yet been identified and is not oxidized in mammalian cells. However, taurine contributes significa...

Mammalian target of rapamycin, mTOR is a serine/threonine kinase that modulates translation in response to growth factors, alterations in nutrient availability and following hypoxia and DNA damage. Here we demonstrate that mTOR activity in Ehrlich Lettré ascites (ELA) cells is transiently increased within minutes following osmotic cell swelling and...

The review describes molecular and functional properties of the volume regulated anion channel and Ca(2+) -dependent Cl(-) channels belonging to the anoctamin family with emphasis on physiological importance of these channels in regulation of cell volume, cell migration, cell proliferation, and programmed cell death. Finally, we discuss the role of...

Multi-drug resistance (MDR) to chemotherapy is the major challenge in the treatment of cancer. MDR can develop by numerous mechanisms including decreased drug uptake, increased drug efflux and the failure to undergo drug-induced apoptosis. Evasion of drug-induced apoptosis through modulation of ion transporters is the main focus of this paper and w...

Anoctamin 6 (ANO6), also known as TMEM16F, has been shown to be a calcium-activated anion channel with delayed calcium activation. The cellular function of ANO6 is under debate, and different groups have come to different conclusions about ANO6's physiological role. Although it is now quite well established that ANO6 is distinct from the volume-reg...

Among the pathophysiological phenotypes defining malignant growth are cell migration and evasion of programmed cell death. The talk will discuss how Cl ⁻ channels affect these processes and how changes in the expression of Cl ⁻ channels are involved in chemotherapy resistance. We investigate the role of the TMEM16 Cl ⁻ channels in cell migration in...

Pathophysiological conditions challenge cell volume homeostasis and perturb cell volume regulatory mechanisms leading to alterations of cell metabolism, active transepithelial transport, cell migration and death. We report that inhibition of the 5-lipoxygenase (5-LO) with AA861 or ETH 615-139, the cysteinyl leukotriene 1 receptor (CysLT1) with the...

Background/aims: Signalling via CysLT1 is involved in activation of volume sensitive K(+) channels and homologous desensitization of the LTD4 receptor impairs regulatory volume decrease (RVD). The aim is to illustrate the effect of mutation of putative PKC consensus phosphorylation sites in the CysLT1R on desensitization and RVD. Methods: mCysLT...

The present work was initiated to investigate regulation of the taurine transporter TauT by reactive oxygen species (ROS) and the tonicity-responsive enhancer binding protein (TonEBP) in NIH3T3 mouse fibroblasts during acute and long-term (4 h) exposure to low-sodium/hypo-osmotic stress. Taurine influx is reduced following reduction in osmolarity,...

Maintaining cell volume is critical for cellular function yet shift in cell volume is a prerequisite for mitosis and apoptosis. The ubiquitously and evolutionary conserved serine/threonine kinase CK2 promotes cell survival and suppresses apoptosis. The present review describes how mammalian cells regulate the cellular content of the major cellular...

Caveolae have been implicated in sensing of cell volume perturbations, yet evidence is still limited and findings contradictory. Here, we investigated the possible role of caveolae in cell volume regulation and volume sensitive signaling in an adipocyte system with high (3T3-L1 adipocytes); intermediate (3T3-L1 pre-adipocytes); and low (cholesterol...

Increased expression of the ubiquitous serine/threonine protein kinase CK2 has been associated with increased proliferative capacity and increased resistance towards apoptosis. Taurine is the primary organic osmolyte involved in cell volume control in mammalian cells, and shift in cell volume is a critical step in cell proliferation, differentiatio...

The accumulation and cytotoxicity of a 10 μmol L⁻¹ equimolar human serum albumin-cisplatin adduct (HSA-Pt) was investigated in suspension Ehrlich Ascites Tumor Cells (EATC) and adherent Ehrlich Lettré Ascites Cells (Lettré). HSA-Pt did not induce apoptosis nor was it taken up by the cells to any significant amount within 24 h incubation. The accumu...

The swelling-activated K(+) currents (I(K,vol)) in Ehrlich ascites tumor cells (EATC) has been reported to be through the two-pore domain (K(2p)), TWIK-related acid-sensitive K(+) channel 2 (TASK-2). The regulatory volume decrease (RVD), following hypotonic exposure in EATC, is rate limited by I(K,vol) indicating that inhibition of RVD reflects inh...

In mammalian cells, the organic osmolyte taurine is accumulated by the Na-dependent taurine transporter TauT and released though the volume- and DIDS-sensitive organic anion channel. Incubating Ehrlich Lettré tumor cells with methyl-β-cyclodextrin (5 mM, 1 h) reduces the total cholesterol pool to 60±5% of the control value. Electron spin resonance...

Platinum compounds are used in the treatment of cancer. We demonstrate that cisplatin-induced (10 μM) apoptosis (caspase-3 activity) is pronounced within 18 hours in non-adherent Ehrlich ascites tumour cells (EATC), whereas there is no increase in caspase-3 activity in the adherent Ehrlich Lettré ascites tumour cells (ELA). Loss of KCl and cell shr...

Changes in cell volume and ion gradients across the plasma membrane play a pivotal role in the initiation of apoptosis. Here we explore the kinetics of apoptotic volume decrease (AVD) and ion content dynamics in wild-type (WT) and multidrug-resistant (MDR) Ehrlich ascites tumor cells (EATC). In WT EATC, induction of apoptosis with cisplatin (5 muM)...

Addition of H(2)O(2) (0.5 mM) to Ehrlich ascites tumor cells under isotonic conditions results in a substantial (22 +/- 1%) reduction in cell volume within 25 min. The cell shrinkage is paralleled by net loss of K(+), which was significant within 8 min, whereas no concomitant increase in the K(+) or Cl(-) conductances could be observed. The H(2)O(2...

The Ca(2+)-independent phospholipase A(2) VI (iPLA(2)-VI) and the Na(+)/H(+) exchanger isoform 1 (NHE1) are highly pH-sensitive proteins that exert both protective and detrimental effects in cardiac ischemia-reperfusion. Here, we investigated the role of extracellular pH (pH(o)) in ischemia-reperfusion injury and death and in regulation and functio...

The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most cases, activation of volume regulatory osmolyte tr...

Cell volume perturbation initiates a wide array of intracellular signalling cascades, leading to protective and adaptive events and, in most cases, activation of volume-regulatory osmolyte transport, water loss, and hence restoration of cell volume and cellular function. Cell volume is challenged not only under physiological conditions, e.g. follow...

Reactive oxygen species (ROS) are produced in NIH3T3 fibroblasts during hypotonic stress, and H(2)O(2) potentiates the concomitant release of the organic osmolyte taurine (Lambert IH. J Membr Biol 192: 19-32, 2003). The increase in ROS production [5-(and-6)-carboxy-2', 7'-dichlorodihydrofluorescein diacetate fluorescence] is detectable after a redu...

Inhibition of the constitutively active casein kinase 2 (CK2) with 2-dimethyl-amino-4,5,6,7-tetrabromo-1H-benzimidasole stimulates the Na(+)-dependent taurine influx via the taurine transporter TauT in NIH3T3 cells. CK2 inhibition reduces the TauT mRNA level and increases the localization of TauT to ER but has no detectable effect on TauT protein e...

The involvement of group VI Ca(2+)-independent PLA(2)s (iPLA(2)-VI) in in vitro ischemia [oxygen and glucose deprivation (OGD)] in mouse C2C12 myotubes was investigated. OGD induced a time-dependent (0-6 h) increase in bromoenol lactone (BEL)-sensitive iPLA(2) activity, which was suppressed by specific short interfering (si)RNA knockdown of iPLA(2)...

Hypotonic exposure provokes the mobilization of arachidonic acid, production of ROS, and a transient increase in taurine release in Ehrlich Lettre cells. The taurine release is potentiated by H(2)O(2) and the tyrosine phosphatase inhibitor vanadate and reduced by the phospholipase A(2) (PLA(2)) inhibitors bromoenol lactone (BEL) and manoalide, the...

The role of phospholipase A2 in the induction of drip loss from pig muscle has been investigated. In samples from porcine M. longissimus dorsi, total PLA2 activity as well as mRNA and protein levels of the group VIA iPLA2 (iPLA2-VIA) increased during the initial 4 h post-mortem period. Morphological studies of porcine muscle showed that at 4 h post...

Murine leukotriene B(4) (LTB(4)) receptor (mBLT1) cDNA was identified by searching the EST database using human LTB(4) receptor as the query sequence. Expression of functional mBLT1 after injection of in vitro transcribed cRNA into Xenopus laevis oocytes was demonstrated as LTB(4)-evoked, Ca(2+)-activated Cl(-) currents recorded by two-electrode vo...

Osmotic swelling of NIH3T3 mouse fibroblasts activates a bromoenol lactone (BEL)-sensitive taurine efflux, pointing to the involvement of a Ca(2+)-independent phospholipase A(2) (iPLA(2)) (Lambert IH. J Membr Biol 192: 19-32, 2003). We report that taurine efflux from NIH3T3 cells was not only increased by cell swelling but also decreased by cell sh...

Phospholipase A2 (PLA2) activity is increased in mammalian cells in response to numerous stimuli such as osmotic challenge, oxidative stress and exposure to allergens. The increased PLA2 activity is seen as an increased release of free, polyunsaturated fatty acids, e.g. arachidonic acid and membrane-bound lysophospholipids. Even though arachidonic...

Swelling-induced taurine efflux from NIH3T3 cells reflects a dependence on volume-sensitive arachidonic acid release. Both iPLA2 and sPLA2 appear to be involved in swelling-induced arachidonic acid release, likely reflecting their specific subcellular localization and dependence on lipid packing rather than volume-induced modulation of the actin-b...

Cell shrinkage is a hallmark of the apoptotic mode of programmed cell death, but it is as yet unclear whether a reduction in cell volume is a primary activation signal of apoptosis. Here we studied the effect of an acute elevation of osmolarity (NaCl or sucrose additions, final osmolarity 687 mosmol l(-1)) on NIH 3T3 fibroblasts to identify compone...

Taurine, present in high concentrations in various mammalian cells, is essential for regulation of cell volume, cellular oxidative status as well as the cellular Ca2+ homeostasis. Cellular taurine content is a balance between active uptake through the saturable, Na(+)-dependent taurine transporter TauT, and passive release via a volume-sensitive le...

The cellular level of the organic osmolyte taurine is a balance between active uptake and passive leak via a volume sensitive pathway. Here, we demonstrate that NIH3T3 mouse fibroblasts express a saturable, high affinity taurine transporter (TauT, Km = 18 microm), and that taurine uptake via TauT is a Na+- and Cl(-)-dependent process with an appare...

The present work sets out to investigate how Ca(2+) regulates the volume-sensitive taurine-release pathway in HeLa cells. Addition of Ca(2+)-mobilizing agonists at the time of exposure to hypotonic NaCl medium augments the swelling-induced taurine release and subsequently accelerates the inactivation of the release pathway. The accelerated inactiva...

Change in the intracellular concentration of osmolytes or the extracellular tonicity results in a rapid transmembrane water flow in mammalian cells until intracellular and extracellular tonicities are equilibrated. Most cells respond to the osmotic cell swelling by activation of volume-sensitive flux pathways for ions and organic osmolytes to resto...

The present study illustrates elements of the signal cascades involved in the activation of taurine efflux pathways in myotubes derived from skeletal muscle cells. Exposing primary skeletal muscle cells, loaded with (14)C-taurine, to 1) hypotonic media, 2) the phospholipase A(2) (PLA(2)) activator melittin, 3) anoxia, or 4) lysophosphatidyl choline...

NIH3T3 mouse fibroblasts generate reactive oxygen species (ROS) and release taurine following exposure to hypotonic medium and to isotonic medium containing the lipase activator melittin. The swelling-induced taurine release is potentiated by H2O2, the calmodulin antagonist W7, and ATP, but inhibited by the antioxidant butulated hydroxytoluene (BHT...

Osmotically swollen NIH3T3 fibroblasts regulate their cell volume towards their initial value just like most mammalian cells1. This back regulation, designated regulatory volume decrease (RVD), is the result of loss of KCl and organic osmolytes1,2. It is estimated that the loss of cellular amino acids constitutes 20% of the total loss of osmolytes...

We demonstrate that two isoforms of the cytosolic phospholipase A2, cPLA2α and cPLA2γ, are present in Ehrlich ascites tumor cells. Both enzymes are almost uniformly distributed throughout the cells under control conditions, as visualized by laser-scanning confocal microscopy. Stimulation by either hypotonic cell swelling or addition of the Ca2+ ion...

In daunorubicin resistant Ehrlich ascites tumor cells (DNR), the initial taurine uptake was reduced by 56% as compared to the parental, drug sensitive Ehrlich cells. Kinetic experiments indicated that taurine uptake in Ehrlich cells occurs via both high- and low-affinity transporters. The maximal rate constant for the initial taurine uptake was red...

The role of Rho GTPases in the regulatory volume decrease (RVD) process following osmotic cell swelling is controversial and has so far only been investigated for the swelling-activated Cl- efflux. We investigated the involvement of RhoA in the RVD process in NIH3T3 mouse fibroblasts, using wild-type cells and three clones expressing constitutively...

It is suggested (i) that following hypotonic exposure, taurine and Cl- leave the HeLa cells via separate main efflux pathways; (ii) the swelling-induced taurine efflux in HeLa cells is increased by addition of extracellular ATP in the μM concentration range, but ATP does not appear to be an autocrine factor in the swelling-induced activation of the...

It has recently been demonstrated that exogenous addition of low concentrations (< 15 microM) of lysophosphatidyl choline (LPC, palmitic acid in the sn-1 position) induces a transient increase in taurine efflux from HeLa cells in a process that seems to involve generation of reactive oxygen species (ROS) and tyrosine phosphorylation (J. Membrane Bi...

Drip loss from porcine muscle (M. longissimus dorsi) contained high concentrations of K(+) ( approximately 135 mM) and organic osmolytes, for example, taurine ( approximately 15 mM), as well as significant amounts of protein ( approximately 125 mg.mL(-1)). Thus, the drip reflects release of intramuscular components. To simulate events taking place...

We demonstrate that two isoforms of the cytosolic phospholipase A2, cPLA2alpha and cPLA2gamma, are present in Ehrlich ascites tumor cells. Both enzymes are almost uniformly distributed throughout the cells under control conditions, as visualized by laser-scanning confocal microscopy. Stimulation by either hypotonic cell swelling or addition of the...

The putative role of lysophospholipids in activation and regulation of the volume-sensitive taurine efflux was investigated in HeLa cells using tracer technique. Lysophosphatidylcholine (LPC, 10 microm) with oleic acid increased taurine efflux during hypotonic and isotonic conditions. Substituting palmitic or stearic acid for oleic acid enhanced ta...

The putative role of lysophospholipids in activation and regulation of the volume-sensitive taurine efflux was investigated in HeLa cells using tracer technique. Lysophosphatidylcholine (LPC, 10 μm) with oleic acid increased taurine efflux during hypotonic and isotonic conditions. Substituting palmitic or stearic acid for oleic acid enhanced taurin...

The present study aimed at elucidating the initial intracellular lysophosphatidic acid (LPA)-induced signaling events, in order to investigate the sequence in which LPA affects the intracellular concentration of free, cytosolic Ca2+, [Ca2+]i , ion channels, the F-actin cytoskeleton, cell volume and the Na+/H+ exchanger. We found that stimulation of...

The supernatant from a suspension of Ehrlich cells exposed to centrifugation at 700×g for 45 s induced a transient increase in the intracellular concentration of free, cytosolic Ca2+, [Ca2+]i, as well as activation of an outwardly rectifying whole-cell current when added to a suspension of non-stimulated cells. These effects were inhibited by suram...

The mechanisms, by which the P2 receptor agonists adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) evoke an increase in the free cytosolic calcium concentration ([Ca2+]i) and in intracellular pH (pHi), have been investigated in Ehrlich ascites tumor cells. The increase in [Ca2+]i evoked by ATP or UTP is abolished after depletion of...

The effect of the phosphatase inhibitor calyculin A (cal A) on the kinetic parameters of the Na+-coupled taurine uptake via the taurine transporter in the Ehrlich ascites tumour cells has been investigated. Preincubation with cal A (100 nM) reduces the initial taurine influx by about 20%, but has no effect on the diffusional component of the taurin...

Taurine plays quantitatively an important role as an organic osmolyte in anisosmotic cell volume regulation in Ehrlich ascites tumour cells3. It is the saturable, pH-sensitive, Na+- and Cl−-dependent β-system that accounts for taurine accumulation9,10,15, whereas the swelling-activated taurine channel accounts for net loss of cellular taurine follo...

Ehrlich ascites tumor cells, loaded with 3H-labeled arachidonic acid and 14C-labeled stearic acid for two hours, were washed and transferred to either isotonic or hypotonic media containing BSA to scavenge the labeled fatty acids released from the cells. During the first two minutes of hypo-osmotic exposure the rate of 3H-labeled arachidonic acid r...

Summary Tetrahymena pyriformis suspended in an inorganic medium accumulates3H-labelled taurine against a concentration gradient resulting in a cellular to extracellular taurine gradient of about 3 within 2 hours. This is observed in spite of the fact that taurine influx inTetrahymena via the saturable, Na1-dependent system and the leak pathway beco...

The putative role for Ca2+ entry and Ca2+ mobilization in the activation of the regulatory volume decrease (RVD) response has been assessed in Ehrlich cells. Following hypotonic exposure (50% osmolarity) there is: (i) no increase in cellular Ins(1,4,5)P3 content, as measured in extracts from [2-3H]myoinositol-labeled cells, a finding at variance wi...

Tetrahymena pyriformis cultivated in the presence of 1 mM taurine prior to transfer of the cells to non-nutrient medium express an enhanced capacity for concentrative taurine uptake and for taurine diffusion compared to cells grown without added taurine. The unidirectional taurine influx in taurine-grown cells comprises a saturable component with K...

Stimulation of Ehrlich ascites tumor cells with leukotriene D4 (LTD4) within the concentration range 1–100 nm leads to a concentration-dependent, transient increase in the intracellular, free Ca2+ concentration, [Ca2+]i . The Ca2+ peak time, i.e., the time between addition of LTD4 and the highest measured [Ca2+]i value, is in the range 0.20 to 0.21...

Stimulation with leukotriene D4 (LTD4) (3–100 nm) induces a transient increase in the free intracellular Ca2+ concentration ([Ca2+]i ) in Ehrlich ascites tumor cells. The LTD4-induced increase in [Ca2+]i is, however, significantly reduced in Ca2+-free medium (2 mm EGTA), and under these conditions stimulation with a low LTD4 concentration (3 nm) do...

The role of 3',5'-cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), protein kinase C (PKC) and phosphatases in the regulation of the taurine influx via the beta-system in Ehrlich ascites tumor cells has been investigated. The taurine uptake by the beta-system in Ehrlich cells is inhibited when PKC is activated by phorbol 12-myristate 1...

The taurine efflux from Ehrlich ascites tumor cells is stimulated by hypotonic cell swelling. The swelling-activated taurine efflux is unaffected by substitution of gluconate for extracellular Cl- but inhibited by addition of MK196 (anion channel blocker) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS; anion channel and anion exchange b...

The swelling-activated Cl- efflux, mediated by the mini Cl- channel (3-7 pS), and the swelling-activated taurine efflux in Ehrlich cells are both inhibited by the anion channel blocker MK196 (indacrinone). The swelling-activated taurine efflux is also inhibited by DIDS and following depolarization of the cell membrane, but it is significantly stimu...

Trypsinized human skin fibroblasts in suspension perform regulatory volume decrease (RVD) after cell swelling in hypotonic medium. During RVD, 36Cl− efflux is dramatically increased and the cell membrane is depolarized, indicating the activation of Cl− channels. This activation of Cl− channels depends on extracellular as well as on intracellular Ca...

HgCl2 (40 μM) initially activates an anion-independent unidirectional Na+ influx in Ehrlich ascites tumor cells, which amounts to 61 ± 7 μmol·g dry wt-1 min-1 (± SEM, n = 5). The unidirectional Na+ influx in control cells in 13 ± 2 μmol·dry wt-1 • min-1 (± SEM, n = 5). The HgCl2-activated Na+ influx is slightly inhibited by amiloride (inhibitor of...

Pretreatment with cytochalasin B, which is known to disrupt microfilaments, significantly inhibits regulatory volume decrease (RVD) in Ehrlich ascites tumor cells, suggesting that an intact microfilament network is a prerequisite for a normal RVD response. Colchicine, which is known to disrupt microtubules, has no significant effect on RVD. Ehrlich...

Taurine influx is inhibited and taurine efflux accelerated when the cell membrane of Ehrlich ascites tumor cells is depolarized. Taurine influx is inhibited at acid pH partly due to the concomitant depolarization of the cell membrane partly due to a reduced availability of negatively charged free carrier. These results are in agreement with a 2Na,1...

The cell membranes of virtually all animal cells are highly permeable to water, and hence the cell volume will be determined by the cellular content of osmotically active solutes and by the osmolality of the extracellular fluid. It should be noted, however, that in epithelial cells only the membrane on the basolateral side is highly water-permeable...

Na and K transport provoked in Ehrlich ascites tumor cells by addition of arachidonic acid is via conductive ion channels and not via any Na+/H+ or K+/H+ exchange systems nor any Cl-dependent cotransport system. The effect of arachidonic acid on the Na conductance is partly mediated via cyclooxygenase metabolites, while the effect on the K conducta...

The fluorescence intensity of the dye 1,1-dipropyloxadicarbocyanine (DiOC3-(5)) has been measured in suspensions of Ehrlich ascites tumor cells in an attempt to monitor their membrane potential (V m ) under different ionic conditions, after treatment with cation ionophores and after hypotonic cell swelling. Calibration is performed with gramicidin...

Electronic cell sizing of Ehrlich ascites tumour cells is presented as a biological test system for assessment of membrane associated effects of toxic compounds. Ehrlich ascites tumour cells readjust their cell volume after osmotic swelling in hypotonic media. This regulatory process (Regulatory Volume Decrease, RVD) involves a net loss of KCl from...

The nature of the leukotriene-D4 (LTD4) induced cell shrinkage in Ehrlich ascites tumor cells has been investigated. LTD4 treatment of Ehrlich cells induces net loss of cellular KCl and cell shrinkage independent of the initial cell volume. LTD4 also produces water loss and reduction in cell volume when all extracellular and all intracellular Cl ha...

The Ehrlich ascites tumor cell has been used as a model of an unspecialized mammalian cell, in an attempt to disclose the mechanisms involved in the regulation of cellular water and salt content. In hypotonic medium Ehrlich cells initially swell as nearly perfect osmometers, but subsequently recover their volume within about 10 min with an associat...

Exposure of Ehrlich cells to isotonic Na+-propionate medium induces a rapid cell swelling. This treatment is likely to impose an acid load on the cells. Cell swelling is absent in K+-propionate medium but may be induced by the ionophore nigericin, which mediates K+/H+ exchange. Cell swelling in Na+-propionate medium is blocked by amiloride, but an...