RESUMEN

The islet in type 2 diabetes is characterized by ß-cell loss, increased ß-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). When protein misfolding protective mechanisms are overcome, human IAPP (h-IAPP) forms membrane permeant toxic oligomers that induce ß-cell dysfunction and apoptosis. In humans with type 2 diabetes (T2D) and mice transgenic for h-IAPP, endoplasmic reticulum (ER) stress has been inferred from nuclear translocation of CCAAT/enhancer-binding protein homologous protein (CHOP), an established mediator of ER stress. To establish whether h-IAPP toxicity is mediated by ER stress, we evaluated diabetes onset and ß-cell mass in h-IAPP transgenic (h-TG) mice with and without deletion of CHOP in comparison with wild-type controls. Diabetes was delayed in h-TG CHOP(-/-) mice, with relatively preserved ß-cell mass and decreased ß-cell apoptosis. Deletion of CHOP attenuates dysfunction of the autophagy/lysosomal pathway in ß-cells of h-TG mice, uncovering a role for CHOP in mediating h-IAPP-induced dysfunction of autophagy. As deletion of CHOP delayed but did not prevent h-IAPP-induced ß-cell loss and diabetes, we examined CHOP-independent stress pathways. JNK, a target of the IRE-1pTRAF2 complex, and the Bcl-2 family proapoptotic mediator BIM, a target of ATF4, were comparably activated by h-IAPP expression in the presence and absence of CHOP. Therefore, although these studies affirm that CHOP is a mediator of h-IAPP-induced ER stress, it is not the only one. Therefore, suppression of CHOP alone is unlikely to be a durable therapeutic strategy to protect against h-IAPP toxicity because multiple stress pathways are activated.

Asunto(s)

Apoptosis , Células Secretoras de Insulina/fisiología , Polipéptido Amiloide de los Islotes Pancreáticos/fisiología , Factor de Transcripción CHOP/genética , Animales , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Estrés del Retículo Endoplásmico , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal , Factor de Transcripción CHOP/metabolismo

RESUMEN

AIMS/HYPOTHESIS: The beta cell transcriptional factor musculoaponeurotic fibrosarcoma oncogene family A (MafA) regulates genes important for beta cell function. Loss of nuclear MafA has been implicated in beta cell dysfunction in animal models of type 2 diabetes. We sought to establish if nuclear MafA is less abundant in beta cell nuclei in humans with type 2 diabetes. METHODS: Pancreas obtained at surgery from five non-diabetic individuals and six individuals with type 2 diabetes was immunostained for insulin, glucagon and MafA. RESULTS: Beta cell nuclear MafA was markedly decreased in type 2 diabetes (1.6 ± 1.2% vs 46.3 ± 8.3%, p < 0.001). CONCLUSIONS/INTERPRETATION: Beta cell nuclear MafA is markedly decreased in humans with type 2 diabetes, which may contribute to impaired beta cell dysfunction.

Asunto(s)

Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Células Secretoras de Insulina/fisiología , Factores de Transcripción Maf de Gran Tamaño/deficiencia , Anciano , Animales , Glucemia/metabolismo , Núcleo Celular/metabolismo , Células Cultivadas , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Femenino , Glucagón/metabolismo , Humanos , Hiperglucemia/metabolismo , Hiperglucemia/fisiopatología , Insulina/metabolismo , Secreción de Insulina , Factores de Transcripción Maf de Gran Tamaño/metabolismo , Masculino , Persona de Mediana Edad , Ratas , Ratas Desnudas

RESUMEN

In type II diabetes (T2DM), there is a deficit in ß-cells, increased ß-cell apoptosis and formation of intracellular membrane-permeant oligomers of islet amyloid polypeptide (IAPP). Human-IAPP (h-IAPP) is an amyloidogenic protein co-expressed with insulin by ß-cells. IAPP expression is increased with obesity, the major risk factor for T2DM. In this study we report that increased expression of human-IAPP led to impaired autophagy, due at least in part to the disruption of lysosome-dependent degradation. This action of IAPP to alter lysosomal clearance in vivo depends on its propensity to form toxic oligomers and is independent of the confounding effect of hyperglycemia. We report that the scaffold protein p62 that delivers polyubiquitinated proteins to autophagy may have a protective role against human-IAPP-induced apoptosis, apparently by sequestrating protein targets for degradation. Finally, we found that inhibition of lysosomal degradation increases vulnerability of ß-cells to h-IAPP-induced toxicity and, conversely, stimulation of autophagy protects ß-cells from h-IAPP-induced apoptosis. Collectively, these data imply an important role for the p62/autophagy/lysosomal degradation system in protection against toxic oligomer-induced apoptosis.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/metabolismo , Autofagia , Proteínas de Choque Térmico/metabolismo , Cuerpos de Inclusión/metabolismo , Células Secretoras de Insulina/metabolismo , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Lisosomas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular , Hiperglucemia/complicaciones , Hiperglucemia/metabolismo , Hiperglucemia/patología , Cuerpos de Inclusión/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/patología , Polipéptido Amiloide de los Islotes Pancreáticos/química , Lisosomas/efectos de los fármacos , Ratones , Obesidad/complicaciones , Obesidad/metabolismo , Obesidad/patología , Fagosomas/efectos de los fármacos , Fagosomas/metabolismo , Sustancias Protectoras/metabolismo , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Estructura Cuaternaria de Proteína , ARN Interferente Pequeño/metabolismo , Ratas , Proteína Sequestosoma-1 , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología

RESUMEN

AIMS/HYPOTHESIS: We sought to establish the relationship between fasting plasma glucose concentrations and pancreatic fractional beta cell area in adult cynomolgus monkeys (Macaca fascicularis). METHODS: Fasting plasma glucose and pancreatic fractional beta cell area were measured in 18 control and 17 streptozotocin-treated adult primates (17.0 +/- 1.2 vs 15.4 +/- 1.2 years old). RESULTS: Fasting plasma glucose was increased (12.0 +/- 2.0 vs 3.4 +/- 0.1 mmol/l, p < 0.01) and fractional beta cell area was decreased (0.62 +/- 0.13% vs 2.49 +/- 0.35%, p < 0.01) in streptozotocin-treated monkeys. The relationship between fasting plasma glucose and pancreatic fractional beta cell area was described by a wide range of beta cell areas in controls. In streptozotocin-treated monkeys there was an inflection of fasting blood glucose at approximately 50% of the mean beta cell area in controls with a steep increase in blood glucose for each further decrement in beta cell area. CONCLUSIONS/INTERPRETATION: In adult non-human primates a decrement in fractional beta cell area of approximately 50% or more leads to loss of glycaemic control.

Asunto(s)

Glucemia/metabolismo , Hiperglucemia/sangre , Células Secretoras de Insulina/patología , Animales , Diabetes Mellitus Experimental/patología , Ayuno , Humanos , Hiperglucemia/patología , Células Secretoras de Insulina/citología , Células Secretoras de Insulina/fisiología , Macaca fascicularis , Masculino

RESUMEN

AIMS/HYPOTHESIS: Beta cell destruction in type 1 diabetes is apparently mediated by the release of cytokines. We questioned whether cytokine-induced apoptosis preferentially kills replicating beta cells. MATERIALS AND METHODS: In the first experiment, rat insulinoma (RIN) cells were studied for 36 h by time-lapse video microscopy. Cells were exposed to three doses of a cytokine mixture (maximal concentration: IL-1beta 50 U/ml; TNF-alpha 1,000 U/ml; IFN-gamma 1,000 U/ml) or vehicle and analysed for the total cell number (2-h intervals) and timing of each cell death and division. In the second experiment, isolated human islets were incubated with the same cytokine mixture for 24 h and examined for replication and paired (postmitotic) apoptosis. RESULTS: In the first experiment, after application of cytokines, apoptosis occurred most frequently immediately after the next or subsequent cell mitosis (p<0.05). In the second experiment, cytokines caused increased apoptosis in human islets, with an increase in the proportion of postmitotic apoptotic pairs (p<0.001). CONCLUSIONS/INTERPRETATION: Cytokine-induced beta cell death preferentially affects newly forming beta cells, which implies that replicating beta cells might be more vulnerable to cytokine destruction. Efforts to expand beta cell mass in type 1 diabetes by fostering beta cell replication are likely to fail unless cytokine-induced apoptosis is concurrently suppressed.

Asunto(s)

Muerte Celular/efectos de los fármacos , Citocinas/farmacología , Células Secretoras de Insulina/citología , Apoptosis/efectos de los fármacos , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Células Secretoras de Insulina/efectos de los fármacos , Microscopía por Video , Persona de Mediana Edad , Mitosis/efectos de los fármacos , Donantes de Tejidos

RESUMEN

Prostaglandins (PG) are released during tissue injury and inflammation, and inhibit immune responses at many points. PG may be one of several factors that protect not only against injury-induced, but also spontaneous, organ-specific autoimmune disease. Here we show that the production of PGE(2), normally produced at a very low rate in islets of Langerhans, is significantly increased in inflamed islets of non-obese diabetic (NOD) mice. We investigated a possible role of PGE(2) in controlling TCR-dependent release of IFN-gamma from islet-reactive NOD CD8(+) T cells. PGE(2) inhibited anti-TCR antibody-triggered release of IFN-gamma from CD8(+) T cell clone 8D8 and from polyclonal cytotoxic T lymphocytes (CTL). Using receptor subtype selective agonists, we present evidence that the effect of PGE(2) is mediated by EP(2) and EP(4) receptors, both of which are coupled to an increase in intracellular cAMP production. The cAMP analogs 8-Br-cAMP and Sp-cAMPS mimic the effect of EP(2)/EP(4) receptor agonists, inhibiting TCR-triggered IFN-gamma release from NOD CD8(+) T cells in a dose-dependent manner. The inhibitory effect of PGE(2) was largely reversed by IL-2 added at the time of culture initiation and decreased with increasing strength of stimulation through the TCR. Resting CTL were more sensitive to PGE(2) than recently expanded CTL and NOD CD8(+) T cells remained insensitive to PGE(2) for a longer time than BALB/c cells. Our study suggests that PGE(2) may be part of a regulatory network that controls local activation of T cells and may play a role in the balance between the development of islet autoimmunity or maintenance of tolerance.

Asunto(s)

Linfocitos T CD8-positivos/fisiología , Diabetes Mellitus Tipo 1/inmunología , Interferón gamma/metabolismo , Receptores de Prostaglandina E/fisiología , Animales , Linfocitos T CD4-Positivos/fisiología , AMP Cíclico/fisiología , Dinoprostona/biosíntesis , Dinoprostona/farmacología , Interleucina-2/farmacología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Receptores de Antígenos de Linfocitos T/fisiología

RESUMEN

Cell-enzyme-linked immunosorbent assay (cell-ELISA) is a technique for the rapid, convenient, and quantitative detection of molecules expressed on the cell surface. Here we present an evaluation of beta-galactosidase as an antibody-tag for cell-ELISA. In contrast to substrates for horseradish peroxidase (HRP) and alkaline phosphatase, murine splenocytes do not hydrolyze the beta-galactosidase substrate chlorophenolred-beta-D-galactopyranoside (CPRG). beta-Galactosidase-antibody conjugates show much lower background binding to murine T cells than conjugates with HRP or alkaline phosphatase. We describe step-by-step procedures for direct and indirect beta-galactosidase based cell-ELISA to quantitate the expression of molecules on the surface of unfixed, live cells. Variations of the basic protocol are suitable for adherent and non-adherent cells, large scale screening for expression of cell surface molecules, and the screening of hybridomas for production of antibodies to cell surface epitopes. Since relatively few beta-galactosidase conjugated antibodies are commercially available, we describe an efficient method to couple beta-galactosidase to antibodies using a novel water soluble heterobifunctional crosslinker, sulfosuccinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate (sulfo-SMCC). We demonstrate the utility of this method by conjugating F(ab')(2) fragments of an anti-B7-2 antibody, and using this conjugate to assay B7-2 on Fc-receptor bearing cells.

Asunto(s)

Ensayo de Inmunoadsorción Enzimática/métodos , beta-Galactosidasa/inmunología , Animales , Antígenos CD/inmunología , Antígeno B7-2 , Células Cultivadas , Fragmentos Fab de Inmunoglobulinas/genética , Fragmentos Fab de Inmunoglobulinas/inmunología , Glicoproteínas de Membrana/inmunología , Ratones , beta-Galactosidasa/genética

RESUMEN

To investigate how CD8+ T cells interact with beta cells and local inflammatory cells in islets, we have isolated CD8+ T cell clones from nonobese diabetic (NOD) spleen that recognize and destroy both islets and the NOD insulinoma cell line NIT-1. The clones destroyed NOD islets with pre-existing inflammation better than islets without signs of inflammation. Islets from NOD-scid mice were destroyed only poorly, but that could be improved by adding IL-7 to the assay. Anti-IFN-gamma Abs inhibited destruction of infiltrated islets. Single islets were effective stimulators of IFN-gamma production by cloned CD8+ T cells, which varied >50-fold depending on the degree of islet infiltration. This effect of the islet mononuclear infiltrate could be mimicked by adding spleen cells to NIT-1 cells, which augmented IFN-gamma production above the level stimulated by NIT-1 cells alone. The enhancing effect of spleen cells could be attributed to their macrophage subpopulation and was not MHC restricted, although recognition of islet Ag by cloned CD8+ T cells and subsequent islet destruction was restricted to islets expressing H-2Db molecules. An inhibitor of inducible NO synthase inhibited destruction of inflamed islets by cloned CD8+ T cells. We propose that macrophages in inflamed islets provide a form of bystander costimulation of beta cell-specific CD8+ T cells. CD8+ T cells respond to Ag and costimulation by producing IFN-gamma that activates macrophages. Activated macrophages facilitate islet destruction by CD8+ T cells through a NO synthesis-dependent pathway.

Asunto(s)

Linfocitos T CD8-positivos/inmunología , Diabetes Mellitus Tipo 1/inmunología , Islotes Pancreáticos/inmunología , Leucocitos Mononucleares/inmunología , Macrófagos/inmunología , Óxido Nítrico/metabolismo , Animales , Movimiento Celular , Células Clonales , Femenino , Antígenos H-2 , Antígeno de Histocompatibilidad H-2D , Antígenos de Histocompatibilidad Clase II/inmunología , Interferón gamma/metabolismo , Islotes Pancreáticos/citología , Activación de Linfocitos , Lisina/análogos & derivados , Lisina/farmacología , Complejo Mayor de Histocompatibilidad , Ratones , Ratones Endogámicos NOD , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II , Transducción de Señal , Bazo/citología , Bazo/inmunología

Asunto(s)

Antígeno HLA-A2/química , Oligopéptidos/química , Agua , Simulación por Computador , Modelos Moleculares , Unión Proteica

RESUMEN

The cytotoxic T cell line CTLL-2 and the T helper cell line HT2 proliferate in response to interleukin 2 (IL-2) or IL-4 without requiring stimulation by antigen through the T cell receptor and therefore lend themselves for studies of IL-2- and IL-4-dependent proliferation and signalling through their cognate receptors. Here we have used CTLL-2 and HT2 cells to investigate the effect of the inflammatory mediator prostaglandin E2 (PGE2) on IL-2- and IL-4-dependent proliferation. PGE2 inhibited IL-2- as well as IL-4-dependent proliferation of both CTLL-2 and HT2 cells, with IL-4-dependent proliferation being more sensitive than IL-2-dependent proliferation and CTLL-2 cells being more sensitive than HT2 cells. A quantitative dose-effect analysis revealed a two-step increase of inhibition (around 10(-10) M and 10(-5) M PGE2) for all combinations of cells and cytokines approaching 100% at high concentrations of PGE2. The data suggest that even in cases where synthesis of IL-2 and IL-4 is differentially affected by PGE2, IL-2- and IL-4-dependent T cells may still be similarly sensitive to PGE2 by way of their cytokine responsiveness. Furthermore, the effects of PGE2 may be mediated by more than one functional binding site or receptor subtype. PGE2 levels are an important consideration when CTLL-2 and HT2 cells are used for the measurement of IL-4 and IL-2.

Asunto(s)

División Celular/fisiología , Dinoprostona/fisiología , Interleucina-2/antagonistas & inhibidores , Interleucina-4/antagonistas & inhibidores , Animales , Línea Celular , Interleucina-2/fisiología , Interleucina-4/fisiología , Ratones

RESUMEN

A cloned Th1 cell line was isolated from pancreatic lymph nodes of NOD mice that carries a T-cell receptor encoding Vbeta14 and proliferates in response to NOD islets, islet supernatant, and crystalline bovine and rat insulin, specifically to a B-chain peptide bound to IA(g7). The response to islet supernatant was reduced by 75% by anti-insulin antibody treatment. The insulin-reactive clone reduced insulitis and totally blocked the development of spontaneous diabetes in NOD mice (n = 8) as well as the adoptive transfer of diabetes into irradiated NOD mice following the injection of splenocytes from diabetic mice (n = 13). Trafficking of the adoptively transferred cells was assessed by labeling the clone or diabetic splenocytes with a fluorescent marker (DiI). The labeled clone was detected in the islet periphery, whereas labeled splenocytes alone invaded the islets by 3 days. In contrast, the protective clone dramatically delayed and reduced the number of labeled diabetic splenocytes infiltrating the islet, although their appearance in the spleen was unaffected. In vitro, the clone as well as supernatant derived from the clone blocked the proliferation of diabetic NOD splenocytes to islets. This inhibitory effect was diminished by anti-transforming growth factor-beta. In conclusion, an insulin-specific Th1 cell was isolated from NOD mice that traffics to the islet and prevents the spontaneous development and the adoptive transfer of diabetes. It appears to act locally by releasing transforming growth factor-beta and/or other factors that inhibit homing to and/or proliferation of diabetic splenocytes within the islet. These findings may provide insights into and suggest mechanisms for the protective effects of insulin therapy against diabetes.

Asunto(s)

Traslado Adoptivo , Antígenos CD4/inmunología , Diabetes Mellitus Tipo 2/prevención & control , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Células TH1/citología , Animales , Bovinos , Moléculas de Adhesión Celular/inmunología , Células Clonales , Citocinas/genética , Diabetes Mellitus Tipo 2/inmunología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Citometría de Flujo , Insulina/farmacología , Ratones , Ratones Endogámicos NOD , Reacción en Cadena de la Polimerasa , ARN/análisis , ARN/genética , Ratas , Organismos Libres de Patógenos Específicos , Células TH1/inmunología , Células TH1/metabolismo

RESUMEN

Hyperosmotic shrinkage (adding 300 microM sucrose to isotonic medium) stimulates lactate and ATP accumulation in rat but not human erythrocytes in which ATP pool was preliminary depleted. Inhibitors of Na(+)-K(+)-2Cl(-)-cotransport, Na+/H(+)- exchange and Na(+)- pump known to be activated by hypertonic medium had no influence on volume-induced effect. EGTA (1 microM), Ca(2+)-ATPase inhibitor vanadate (200 microM) and antagonist of calmodulin R24571 (10 microM) suppressed the stimulation of glycolysis by 80 and 30%, respectively. Addition of 1 microM Ca2+ and 1 mM Ca(2+)-ionophore A23187 in Ca2+ free medium stimulated glycolysis by 20% at isotonic conditions while additional hyperosmotic shrinkage resulted in a two-fold activation. It is suggested that shrinkage regulates activity of glycolytic enzymes through the mechanism of intracellular signaling involving Ca2+.

Asunto(s)

Eritrocitos/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Calcimicina/farmacología , ATPasas Transportadoras de Calcio/antagonistas & inhibidores , Calmodulina/antagonistas & inhibidores , Proteínas Portadoras/antagonistas & inhibidores , Ácido Egtácico/farmacología , Glucólisis , Humanos , Lactatos/metabolismo , Ácido Láctico , Proteínas de la Membrana/antagonistas & inhibidores , Presión Osmótica , Ratas , Intercambiadores de Sodio-Hidrógeno/antagonistas & inhibidores , Simportadores de Cloruro de Sodio-Potasio , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores

RESUMEN

The kinetics of the volume-dependent activation of Na+/H+ exchange, Na+,K+,2Cl(-)-cotransport and K+,Cl(-)-cotransport in rat erythrocytes was studied. The significant increase in the rate of Na+/H+ exchange is observed within 15 min after hypertonic shrinkage while the maximum transport rate is reached by 20 min. A delay of about 5 min was found in activation of Na+,K+,2Cl(-)-cotransport, the maximum transport rate being reached 10 min after shrinkage. Activation of K+,Cl(-)-cotransport by hypotonic swelling was registered within 10 min after cell swelling, with a simultaneous achievement of the constant transport rate. Preincubation of cells at 49 degrees C has no effect on the basal Na+/H+ exchange and Na+,K+,2Cl(-)-cotransport but suppresses the activation of these systems by osmotic shrinkage. On the contrary, the rate of K+,Cl(-)-cotransport in isosmotic medium is raised 10-fold after preincubation at 49 degrees C. The thermal treatment at 49 degrees C blocks the activation of K+,Cl(-)-cotransport by swelling. On the basis of the data on thermal denaturation of spectrin at the same temperature it was suggested that the cytoskeleton of erythrocyte membrane is involved in volume regulation of the ion-transporting systems and that the molecular mechanisms which underlie the activation of Na+/H+ exchange, Na+,K+,2Cl(-)-cotransport and K+,Cl(-)-cotransport are essentially different.

Asunto(s)

Proteínas Portadoras/metabolismo , Eritrocitos/metabolismo , Calor , Transporte Iónico , Animales , Cloruros/metabolismo , Volumen de Eritrocitos , Cinética , Proteínas de la Membrana/metabolismo , Concentración Osmolar , Potasio/metabolismo , Desnaturalización Proteica , Ratas , Radioisótopos de Rubidio , Sodio/metabolismo , Intercambiadores de Sodio-Hidrógeno , Simportadores de Cloruro de Sodio-Potasio , Temperatura

RESUMEN

The rates of 86Rb influx into human and rat erythrocytes were studied in media of various tonicity. At sucrose concentrations below 0.3 mol/l, the ouabain-insensitive, furosemide-inhibited component of influx increased in rat but not in human erythrocytes; this may be explained by a rise in the rate of Na+, K+, Cl-- and/or K+, Cl-cotransport. An increase in osmolarity resulted in a reduction of this as well as of the ouabain and furosemide-insensitive component in rat erythrocytes. At the same conditions a drastic inhibition of Na+, K(+)-pump occurred both in rat and human erythrocytes. We failed to observe a lag-phase in the activation of the cotransport in rat erythrocytes; i. e. the process of activation parallels the shrinkage of cells. In rat erythrocyte ghosts, the shrinkage-induced stimulation of the cotransport was lost, and the direction of their osmotic reaction (inhibition of transport pathways) was similar to that in human erythrocyte ghosts. It is suggested that the mechanism of volume regulation of ion transport in intact cells involves a step of physical amplification via a change in interactions between the protein carcass and the lipid bilayer.

Asunto(s)

Eritrocitos/metabolismo , Potasio/sangre , Animales , Transporte Biológico Activo/efectos de los fármacos , Cloruros/sangre , Eritrocitos/efectos de los fármacos , Femenino , Furosemida/farmacología , Humanos , Técnicas In Vitro , Presión Osmótica , Ouabaína/farmacología , Ratas , Ratas Endogámicas WKY , Rubidio/sangre , Sodio/sangre , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , ATPasa Intercambiadora de Sodio-Potasio/sangre

RESUMEN

The review deals with literature and our own experimental data on the possible mechanisms of activation of the ion transport in cells during the change of their volume. The involvement in this process of calcium, cyclic mononucleotides, metabolites of polyphosphoinositides and arachidonic acid, as well as the membrane carcass and cytoskeleton are discussed.

Asunto(s)

Células/metabolismo , Animales , Ácido Araquidónico/metabolismo , Transporte Biológico/fisiología , Calcio/metabolismo , Membrana Celular/metabolismo , Citoesqueleto/metabolismo , Nucleótidos Cíclicos/metabolismo , Fosfatidilinositoles/metabolismo , Proteínas Quinasas/metabolismo