Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Permeability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1978

The effect of cyclic nucleotides and protein phosphorylation on the permeability of human erythrocyte ghosts to certain cations.

Preparations of human erythrocyte membranes have been made which are in the form of sealed vesicles and which behave as osmometers on suspension in solutions of simple inorganic salts. Using these preparations the permeability of the membranes to Na+, K+, Mg2+ and Ca2+ was measured. Cyclic AMP (but not cyclic GMP) increased the permeability of the membranes to Ca2+ with a half maximal effect at a concentration of 25 microgram but did not affect the permeability to the other ions tested. Phosphorylation of proteins in the erthrocyte membrane lowered the permeability to Ca2+ without affecting the permeability to the other ions tested and there was a good correlation between the time course of protein phosphorylation and decrease in Ca2+ permeability. It is postulated that the system through which cyclic AMP causes an initial rapid rise in Ca2+ permeability followed by increased phosphorylation of membrane proteins and reduced Ca2+ permeability may have a widespread occurrence in biological systems and serve to control the concentration of Ca2+ in the cytoplasm.

Calcium↗
PubMed1986

Permeability of small nonelectrolytes through lipid bilayer membranes.

Diffusion of small nonelectrolytes through planar lipid bilayer membranes (egg phosphatidylcholine-decane) was examined by correlating the permeability coefficients of 22 solutes with their partition coefficients between water and four organic solvents. High correlations were observed with hexadecane and olive oil (r = 0.95 and 0.93), but not octanol and ether (r = 0.75 and 0.74). Permeabilities of the seven smallest molecules (mol wt less than 50) (water, hydrofluoric acid, hydrochloric acid, ammonia, methylamine, formic acid and formamide) were 2- to 15-fold higher than the values predicted by the permeabilities of the larger molecules (50 less than mol wt less than 300). The "extra" permeabilities of the seven smallest molecules were not correlated with partition coefficients but were inversely correlated with molecular volumes. The larger solute permeabilities also decreased with increasing molecular volume, but the relationship was neither steep nor significant. The permeability pattern cannot be explained by the molecular volume dependence of partitioning into the bilayer or by the existence of transient aqueous pores. The molecular volume dependence of solute permeability suggests that the membrane barrier behaves more like a polymer than a liquid hydrocarbon. All the data are consistent with the "solubility-diffusion" model, which can explain both the hydrophobicity dependence and the molecular volume dependence of nonelectrolyte permeability.

Carbon Radioisotopes↗
PubMed1985

Relationship between fluidity and ionic permeability of bilayers from natural mixtures of phospholipids.

Proton and calcium permeability coefficients of large unilamellar vesicles made from natural complex mixtures of phospholipids were measured in various conditions and related to membrane fluidity. Permeability coefficients at neutral pH and 25 degrees C were in the range of 10(-4) cm sec-1 and 2.5 X 10(-11) cm sec-1 for protons and calcium, respectively. With the exception of two cases, (H+) greater than 10(-4) M and (Ca2+) greater than 10(-3) M, fluidity increases correspond to permeability increases. Theoretical analysis shows that, for both ions, the measured values of permeability coefficients imply that the permeation process is controlled by the product D1D2 of the diffusion coefficient from the medium into the membrane (D1) by the diffusion coefficient in the membrane (D2). Further analysis of D1 values deduced from combined use of permeability and fluidity data shows that the solubilization should occur in a medium of dielectric constant of about 12, suggesting the involvement of the hydration water of membranes. High proton concentrations, although having virtually no effect on fluidity, trigger the appearance of lateral heterogeneity in membranes, as seen by 31P NMR, and large permeability increases. It is proposed that the main effect of fluidity and/or lateral heterogeneity on permeability may be via the membrane hydration control. We conclude that the current assumption that permeability is controlled by fluidity should be regarded with caution, at least in the case of ions and natural mixtures of phospholipids.

Calcium↗
PubMed1979

Ca2+ control of electrolyte permeability in plasma membrane vesicles from cat pancreas.

The influence of Ca2+ and other cations on electrolyte permeability has been studied in isolated membrane vesicles from cat pancreas. Ca2+ in the micromolar to millimolar concentration range, as well as Mg2+, Sr2+, Mn2+ and La3+ at a tested concentration 10(-4) M, increased Na+ permeability when applied at the vesicle inside. When added to the vesicle outside, however, they decreased Na+ permeability. Ba2+ was effective from the outside but not from the vesicle inside. When Ca2+ was present at both sides of the membrane, Na+ efflux was not affected as compared to that in the absence of Ca2+. Monovalent cations such as Rb+, Cs+, K+, Tris+ and choline+ decreased Na+ permeability when present at the vesicle outside at a concentration range of 10 to 100 mM. Increasing Na+ concentrations from 10 to 100 mM at the vesicle inside increased Na+ permeability. The temperature dependence of Na+ efflux revealed that the activation energy increased in the lower temperature range (0 to 10 degrees C) when Ca2+ was present at the outside or at both sides, but not when present at the vesicle inside only or in the absence of Ca2+. The results suggest that the Ca2+ outside effect is due to binding of calcium to negatively charged phospholipids with a consequent reduction of both fluidity and Na+ permeability of the membrane. The Ca2+-inside effect most likely involves interaction with proteins with consequent increase in Na+ permeability. The data are consistent with current hypotheses on secretagogue-induced fluid secretion in acinar cells of the pancreas according to which secretagogues elicit NaCl and fluid secretion by liberating Ca2+ from cellular membranes and by stimulating Ca2+ influx into the cell. The increased intracellular Ca2+ concentration in turn increases the contraluminal Na+ permeability which leads to NaCl influx. The luminal sodium pump finally transports Na+ ions into the lumen.

Animals↗
PubMed2006

Increased colorectal permeability in patients with severe sepsis and septic shock.

OBJECTIVE: To develop a method for the assessment of colorectal permeability in septic patients. DESIGN AND SETTING: Observational study in ICUs at two university hospitals. PARTICIPANTS: Nine patients with septic shock and abdominal focus of infection, 7 with severe sepsis and pulmonary focus and 8 healthy subjects. MEASUREMENTS AND RESULTS: Colorectal permeability was assessed as the initial appearance rate of (99m)Tc-DTPA in plasma after instillation into the rectal lumen and as the cumulative systemic recovery at 1h. To calculate the latter, volume of distribution and renal clearance of (99m)Tc-DTPA was estimated by an i.v. bolus of (51)Cr-EDTA. The initial rate of permeability was increased in patients with septic shock and severe sepsis compared with controls [29.0 (3.7-83.3), 20.6 (3.6-65.5) and 6.0 (2.2-9.6)cpm ml(-1)min(-1), respectively, p<0.05)] with a positive linear trend (r (2)=0.27, p=0.01) and correlated to L-lactate concentrations in the rectal lumen (r (2)=0.39, p<0.05). The cumulative permeability was also increased in patients with septic shock and severe sepsis compared with controls [2.07 (0.05-15.7), 0.32 (0.01-1.2) and 0.03 (0.01-0.06) per thousand, respectively, p<0.01] and correlated to the initial permeability rate (r (2)=0.26, p=0.01). CONCLUSIONS: In septic patients, the systemic recovery of a luminally applied marker of paracellular permeability was increased and related to the luminal concentrations of L-lactate and possibly to disease severity. This suggests that the assessment of colorectal permeability by systemic recovery of (99m)Tc-DTPA is valid and that metabolic dysfunction of the mucosa contributes to increased permeability of the large bowel in patients with severe sepsis and septic shock.

Adult↗
PubMed2004

Studies on water transport through the sweet cherry fruit surface: IX. Comparing permeability in water uptake and transpiration.

Water uptake and transpiration were studied through the surface of intact sweet cherry (Prunus avium L.) fruit, exocarp segments (ES) and cuticular membranes (CM) excised from the cheek of sweet cherry fruit and astomatous CM isolated from Schefflera arboricola (Hayata) Hayata, Citrus aurantium L., and Stephanotis floribunda Brongn. leaves or from Lycopersicon esculentum Mill. and Capsicum annuum L. var. annuum Fasciculatum Group fruit. ES and CM were mounted in diffusion cells. Water (deionized) uptake into intact sweet cherry fruit, through ES or CM interfacing water as a donor and a polyethyleneglycol (PEG 6000, osmotic pressure 2.83 MPa)-containing receiver was determined gravimetrically. Transpiration was quantified by monitoring weight loss of a PEG 6000-containing donor (2.83 MPa) against dry silica as a receiver. The permeability coefficients for osmotic water uptake and transpiration were calculated from the amount of water taken up or transpired per unit surface area and time, and the driving force for transport. Permeability during osmotic water uptake was markedly higher than during transpiration in intact sweet cherry fruit (40.2-fold), excised ES of sweet cherry fruit (12.5- to 53.7-fold) and isolated astomatous fruit and leaf CM of a range of species (on average 23.0-fold). Partitioning water transport into stomatal and cuticular components revealed that permeability of the sweet cherry fruit cuticle for water uptake was 11.9-fold higher and that of stomata 56.8-fold higher than the respective permeability during transpiration. Increasing water vapor activity in the receiver from 0 to 1 increased permeability during transpiration across isolated sweet cherry fruit CM about 2.1-fold. Permeability for vapor uptake from saturated water vapor into a PEG 6000 receiver solution was markedly lower than from liquid water, but of similar magnitude to the permeability during self-diffusion of (3)H(2)O in the absence of osmotica. The energy of activation for self-diffusion of water across ES or CM was higher than for osmotic water uptake and decreased with increasing stomatal density. The data indicate that viscous flow along an aqueous continuum across the sweet cherry fruit exocarp and across the astomatous CM of selected species accounted for the higher permeability during water uptake as compared to self-diffusion or transpiration.

Biological Transport↗
PubMed2001

Effect of humidity on cuticular water permeability of isolated cuticular membranes and leaf disks.

The effects of humidity on water permeability of astomatous, isolated cuticular membranes and leaf disks of Citrus aurantium L., Vinca major L., Prunus laurocerasus L., Hedera helix L. and Forsythia intermedia (Thunb.) Vahl. were investigated by a new method using 3H2O. With isolated cuticular membranes of P. laurocerasus the isotope method resulted in values similar to those obtained by a well-established gravimetric method. Cuticular water permeability significantly increased by factors of 2 to 3 when air humidities increased from 2 to 100%. Plots of permeances vs. air humidity were non-linear and the slope increased with increasing air humidity. Permeances of intact leaf disks showed a response to increasing humidity similar to those of isolated cuticular membranes. When cuticular water permeability was measured using wax-free, isolated polymer matrix membranes that had been methylated, the effect of air humidity was significantly suppressed compared to non-methylated polymer matrix membranes. From this observation it is concluded that non-esterified, free carboxyl groups present in the cutin polymer matrix significantly contribute to the effect of humidity on cuticular water permeability. These and other polar groups sorb water, which in turn increases the water permeability of polar domains of the cuticle. This humidity-sensitive, polar path of cuticular water permeability is arranged in parallel with the major, dominating and humidity-independent, non-polar path of cuticular water permeability formed by the lipophilic wax components of the cuticle. This conclusion is supported by the fact that cuticular transpiration can be increased by orders of magnitude upon (i) wax extraction, (ii) increase in temperature or (iii) the action of plasticizers, none of which influenced or only marginally influenced the permeability of inorganic ions penetrating plant cuticles across humidity-sensitive polar pores.

Biological Transport↗
PubMed1983

Cadmium and thallous ion permeabilities through lipid bilayer membranes.

Cadmium (Cd2+) and thallous ion (Tl+) permeabilities were measured in planar (Mueller-Rudin) lipid bilayer membranes made from diphytanoylphosphatidylcholine in decane. Permeabilities of the electroneutral Cl- complexes, measured with tracers (109Cd and 204Tl), were about 10(-8) cm X s-1 for CdCl2 and 10(-6) cm X s-1 for TlCl. Electrical conductance measurements showed that permeabilities to Cd2+ and Tl+ were approx. 10(-11) cm X s-1, similar to the Na+ permeability. The low permeabilities to both Cd2+ and CdCl2 are consistent with biological studies which suggest that Cd transport and toxicity are protein mediated and correlated with Cd2+, not CdCl2, concentration. However, the low bilayer permeability to Tl+ raises questions about recent reports that Tl+ is a lipid permeable cation in biological membranes and liposomes. An alternative explanation for the lipid permeable behavior of Tl+ is presented, based on the diffusion of TlCl and other complexes of Tl+ with inorganic and organic anions.

Cadmium↗
PubMed1993

Optical imaging of Cl- permeabilities in normal and CFTR-expressing mouse L cells.

Single cell optical imaging techniques were used to compare Cl- conductances in cystic fibrosis transmembrane conductance regulator (CFTR)-expressing and control mouse L cell fibroblasts. Elevation of intracellular cAMP levels in control cells was without effect on plasma membrane Cl- permeability, whereas cells engineered to stably express CFTR displayed a 20-fold enhancement of plasma membrane Cl- permeability in response to cAMP. Control L cells displayed Ca(2+)-, as well as swelling-activated Cl- permeabilities, which were small compared with cAMP-stimulated permeability in CFTR-expressing cells. CFTR-expressing cells also displayed a similar swelling-activated Cl- permeability. Whereas 50% of the CFTR-expressing cells possessed a small Ca(2+)-activated Cl- permeability similar to control cells, the other cells displayed an enhanced response which was never observed in control cells. Intracellular cAMP determinations suggested that this latter result might be explained by a Ca(2+)-induced rise of cAMP. The cAMP-activated and Ca(2+)-activated Cl- conductances had different anion selectivities, as measured by light scattering of suspended cells. Activation of protein kinase C was without effect on Cl- permeability in CFTR-expressing cells, nor did it modify cAMP-activation of Cl- permeability. Thus, expression of human CFTR in L cells does not confer cAMP-sensitivity to pre-existing, endogenous Ca(2+)- or swelling-activated Cl- channels, but rather confers a novel Cl- conductance which is regulated by cAMP. Osmotic cell swelling and PKC activation are without specific effect in CFTR-expressing L cells. However, elevated [Ca2+]i may play a role in activating a Cl- conductance specifically associated with CFTR.

Animals↗
PubMed1984

Changes in airway permeability and responsiveness after exposure to ozone.

The purpose of this investigation was to examine the relationship between airway responsiveness and the permeability of histamine through the airways in conscious sheep after exposure to ozone (O3). Airway responsiveness was assessed by measuring the change from baseline in mean pulmonary flow resistance following a controlled 2-min inhalation challenge with 1% histamine, containing 200 microCi/ml of [3H]histamine. The rate of appearance of the [3H]histamine in the plasma during inhalation challenge was used to estimate airway permeability. To perturb the airways, conscious sheep were exposed to either 0.5 or 1.0 ppm O3 for 2 hr via an endotracheal tube. Airway responsiveness and airway permeability were measured prior to and 1 day after exposure. In six sheep exposed to 0.5 ppm O3, increased airway responsiveness and airway permeability were observed 1 day after exposure. Four of seven sheep exposed to 1.0 ppm O3 had enhanced airway responsiveness and airway permeability, while the remaining three sheep showed corresponding decreases in airway responsiveness and airway permeability. Since the O3-induced directional changes in airway responsiveness paralleled the directional changes in airway permeability in both the positive and negative directions, it was concluded that changes in airway responsiveness to inhaled histamine following exposure to O3 may be related to concomitant changes in airway permeability to this agent.

Airway Resistance↗
PubMed1992

Effect of breeding state, moulting, dehydration, exposure to saturated atmosphere, and arginine vasotocin on cutaneous water permeability in the toad Bufo bufo.

Cutaneous water permeability was assessed in hydrated male toads under a variety of conditions, including dehydration and rehydration, and the effects of exogenous arginine vasotocin (AVT) were determined. Cutaneous water permeability (the rate of water uptake by toads in water) was high in toads collected in the breeding pond and declined steeply during the first week, coincident with reduced activity of the cutaneous mucus glands. The slopes of the dose-response curves relating AVT to cutaneous water influx were about the same at the transition from the breeding to the nonbreeding state, but the level of influx was higher in the breeding state. The dose-response relationship in long-term terrestrial-acclimated toads was similar to that in water-acclimated toads. The threshold dose for effect on the cutaneous water permeability was about 1 ng AVT. Dehydration had a substantially greater effect on the cutaneous water permeability than AVT. The ratio between dehydration and AVT responses tended to increase with increasing water transport capacity of the skin. Moulting and acclimation to a saturated atmosphere in fully hydrated toads more than doubled the water permeability and abolished the response to AVT. It is suggested that AVT and other factors increase the cutaneous water permeability by similar mechanisms, such as insertion of water channels in the apical membrane of the epidermal cells. The effect of AVT on the toad skin is interpreted as reflecting the general high potency of neurohypophysial hormones in stimulating the water permeability of membranes of variable permeability.

Acclimatization↗
PubMed1993

Intestinal permeability and the prediction of relapse in Crohn's disease.

To see whether intestinal permeability (IP) predicted relapse in Crohn's disease, we measured IP in 72 patients with quiescent Crohn's disease using the lactulose-mannitol test. The permeability index (lactulose/mannitol) was significantly higher in patients than in controls (0.046 [SEM 0.005] vs 0.018 [SEM 0.002], respectively). Patients were followed for 1 year after the test. 26 of the 37 patients with raised permeability, but only 6 of the 35 with normal permeability relapsed within 1 year after the test (p < 0.001). The sensitivity of the permeability test as a predictor for relapse was 81%. A significant correlation was found between the value of the permeability index and the probability of relapse (p < 0.01). These results show that increases in intestinal permeability precede clinical relapses in Crohn's disease and so are an indicator of subclinical disease. The measurement of intestinal permeability may lead to a better understanding of the pathogenesis of Crohn's disease.

Adult↗
PubMed2004

Role of mitochondrial permeability transition pores in mitochondrial autophagy.

During autophagy, cells rid themselves of damaged and superfluous mitochondria, as well as other organelles. This activation of mitochondrial turnover could be the result of changes in the physiological state of mitochondria. Confocal microscopy and fluorescence techniques indicate that onset of mitochondrial permeability transition is one such change. The mitochondrial permeability transition is a reversible phenomenon whereby the mitochondrial inner membrane becomes freely permeable to solutes of less than 1500 Da. At onset of the mitochondrial permeability transition, mitochondria depolarize, uncouple, and undergo large amplitude swelling due to opening of permeability transition pores, which may form by aggregation of damaged, misfolded membrane proteins. When injurious cellular stresses occur, cells may protect themselves using autophagy to remove damaged mitochondria and mutated mitochondrial DNA. Ca(2+) overloading, reactive oxygen and nitrogen species, decreased mitochondrial membrane potential, and oxidation of pyridine nucleotides and glutathione all promote mitochondrial damage and onset of the mitochondrial permeability transition. The mitochondrial permeability transition is also associated with necrosis and apoptosis after a variety of stimuli. This review emphasizes the role of the mitochondrial permeability transition as a key event in mitochondrial autophagy.

Aging↗
PubMed2006

Anthranoid laxatives influence the absorption of poorly permeable drugs in human intestinal cell culture model (Caco-2).

Interactions between widely used anthranoid laxatives and other simultaneously administered drugs are not known. In this paper, the influence of rhein, danthron, sennidins A/B, sennosides A/B, and senna leaf infusion was investigated on the permeability of furosemide, ketoprofen, paracetamol, propranolol, verapamil, digoxin, and Rhodamine 123 across Caco-2 monolayers. The effects on monolayer integrity ([(14)C]mannitol permeability, TEER) were also determined. The in vitro absorption of highly permeable drugs was not strongly affected during co-administration of the laxatives. Furosemide permeability was enhanced by rhein and danthron (3.6 and 3.0-fold), which may partly be due to opening of the paracellular spaces and/or effects on active efflux. However, the secretory permeability of digoxin and Rho 123 was not strongly affected by rhein and danthron, suggesting that inhibition of MDR1 was not responsible for the increased permeation of furosemide. The absorptive permeability of digoxin was decreased by rhein and danthron, offering evidence for effects on apical membranes. The effects on monolayer integrity were detectable, but reversible. According to presented experiments, daily use of laxatives with well-absorbing drugs would seem unlikely to affect drug permeability, but the effects on the absorption of poorly permeable drugs cannot be excluded.

Absorption↗
PubMed2006

Molecular expression and functional involvement of the bovine calcium-activated chloride channel 1 (bCLCA1) in apical HCO3- permeability of bovine corneal endothelium.

Corneal endothelium secretes HCO(3)(-) from basolateral (stroma) to apical (anterior chamber) compartments. Apical HCO(3)(-) permeability can be enhanced by increasing [Ca(2+)](i). We hypothesized that the bovine calcium-activated chloride channel 1 (bCLCA1), shown previously by PCR screening to be expressed in corneal endothelium, is involved in Ca(2+) activated apical HCO(3)(-) permeability. bCLCA1 expression in cultured bovine corneal endothelial cells (CBCEC) was examined by in situ hybridization analysis, immunoblotting, immunofluorescence and confocal microscopy. Rabbit polyclonal antibodies were generated using a 14 aa polypeptide (417-430) from the predicted sequence of bCLCA1. The small interference RNA (siRNA) knock down technique was used to evaluate the functional involvement of bCLCA1 in apical HCO(3)(-) permeability. In situ hybridization confirmed prominent bCLCA1-specific mRNA expression in CBCEC. bCLCA1 antiserum detected the heterologously expressed bCLCA1 in HEK293 cells and a 90kDa band in CBCEC, which was absent when using the pre-immune serum or antigen absorption of serum. Immunofluoresence staining with anti-bCLCA1 antibody and confocal microscopy indicates an apical membrane location in CBCEC. In CBCEC transfected with bCLCA1 specific siRNA, bCLCA1 expression was reduced by 80%, while transfection with siControl scrambled sequence had no effect. Increasing [Ca(i)(2+)] by application of ATPgammaS or cyclopiazonic acid (CPA) increased apical HCO(3)(-) permeability in siControl transfected CBCEC, while having no effect on apical HCO(3)(-) permeability in bCLCA1 specific siRNA transfected cells. Baseline HCO(3)(-) permeability, however, was not different between controls and siRNA treated cells. We conclude that the calcium-activated chloride channel (bCLCA1) is expressed in bovine corneal endothelial cells and can contribute to Ca(2+) dependent apical HCO(3)(-) permeability, but not resting permeability, across the corneal endothelium.

Animals↗
PubMed2005

Validation of the 96 well Caco-2 cell culture model for high throughput permeability assessment of discovery compounds.

The use of Caco-2 cells for permeability screening of discovery compounds is quite well established and serves as the "method-of-choice" across the pharmaceutical industries worldwide. The typical permeability-screening model involves growing cells on a 12 well or 24 well transwell format. In this manuscript, we report the use of Caco-2 cells grown on 96 well transwell plates for screening of discovery compounds to assess their permeability characteristics. A set of standard compounds (marketed compounds) belonging to the various class of Biopharmaceutics Classification System (BCS) were used to assess the utility of the 96 well Caco-2 cells. Extensive validations were also performed with approximately 160 Bristol-Myers Squibb (BMS) discovery compounds by comparing the permeability values in the 96 well Caco-2 cells with the in-house 24 well Caco-2 cells. Functional Caco-2 cells with intact monolayers could be established in the 96 well format using optimized seeding and culturing conditions. The permeability of BCS compounds in the 96 well format was found to be comparable to the permeability in 24 well format. Similarly, there was very good correlation (R2=0.93) between the two formats for the extensive validation performed with in-house discovery compounds. The validated 96 well Caco-2 cell system presents a very attractive permeability screening tool that can perform much more efficiently than the conventional 12 well or 24 well systems while providing the same high quality permeability screening data.

Automation↗
PubMed2004

Cysteinyl leukotriene receptor antagonist regulates vascular permeability by reducing vascular endothelial growth factor expression.

BACKGROUND: Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Cysteinyl leukotrienes (cysLTs) potently elicit increased vascular permeability in airways, leading to airway edema. Vascular endothelial growth factor (VEGF) is 1 of the most potent proangiogenic cytokines and also increases vascular permeability so that plasma proteins can leak into the extravascular space. However, the mechanisms by which cysLTs induce increased vascular permeability are not clearly understood. OBJECTIVE: An aim of the current study was to determine the role of the cysLTs, more specifically in the increase of vascular permeability. METHODS: We used a BALB/c mouse model of allergic asthma to examine effects of cysLT receptor antagonists on bronchial inflammation and airway hyperresponsiveness, more specifically on the increase of vascular permeability. RESULTS: These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of VEGF. Administration of cysLT receptor antagonists markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. CONCLUSION: These results indicate that cysLT receptor antagonists modulate vascular permeability by reducing VEGF expression and suggest that cysLT receptor may regulate the VEGF expression.

Acetates↗
PubMed1997

Permeability of acetic acid across gel and liquid-crystalline lipid bilayers conforms to free-surface-area theory.

Solubility-diffusion theory, which treats the lipid bilayer membrane as a bulk lipid solvent into which permeants must partition and diffuse across, fails to account for the effects of lipid bilayer chain order on the permeability coefficient of any given permeant. This study addresses the scaling factor that must be applied to predictions from solubility-diffusion theory to correct for chain ordering. The effects of bilayer chemical composition, temperature, and phase structure on the permeability coefficient (Pm) of acetic acid were investigated in large unilamellar vesicles by a combined method of NMR line broadening and dynamic light scattering. Permeability values were obtained in distearoylphosphatidylcholine, dipalmitoylphosphatidylcholine, dimyristoylphosphatidylcholine, and dilauroylphosphatidylcholine bilayers, and their mixtures with cholesterol, at various temperatures both above and below the gel-->liquid-crystalline phase transition temperatures (Tm). A new scaling factor, the permeability decrement f, is introduced to account for the decrease in permeability coefficient from that predicted by solubility-diffusion theory owing to chain ordering in lipid bilayers. Values of f were obtained by division of the observed Pm by the permeability coefficient predicted from a bulk solubility-diffusion model. In liquid-crystalline phases, a strong correlation (r = 0.94) between f and the normalized surface density sigma was obtained: in f = 5.3 - 10.6 sigma. Activation energies (Ea) for the permeability of acetic acid decreased with decreasing phospholipid chain length and correlated with the sensitivity of chain ordering to temperature, [symbol: see text] sigma/[symbol: see text](1/T), as chain length was varied. Pm values decreased abruptly at temperatures below the main phase transition temperatures in pure dipalmitoylphosphatidylcholine and dimyristoylphosphatidylcholine bilayers (30-60-fold) and below the pretransition in dipalmitoylphosphatidylcholine bilayers (8-fold), and the linear relationship between in f and sigma established for liquid-crystalline bilayers was no longer followed. However, in both gel and liquid-crystalline phases in f was found to exhibit an inverse correlation with free surface area (in f = -0.31 - 29.1/af, where af is the average free area (in square angstroms) per lipid molecule). Thus, the lipid bilayer permeability of acetic acid can be predicted from the relevant chain-packing properties in the bilayer (free surface area), regardless of whether chain ordering is varied by changes in temperature, lipid chain length, cholesterol concentration, or bilayer phase structure, provided that temperature effects on permeant dehydration and diffusion and the chain-length effects on bilayer barrier thickness are properly taken into account.

1,2-Dipalmitoylphosphatidylcholine↗