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PubMed1995

Increased permeability of phase-separated liposomal membranes with mixtures of ethanol-induced interdigitated and non-interdigitated structures.

It has been suggested by many workers using model membranes that the interdigitated structure formation, in which the acyl chains fully interpenetrate the hydrocarbon chains of the opposing monolayer, plays an important role in regulating many functions of biomembranes. In the present study the control of permeability was focused on as one of the biomembrane functions, and the effects of ethanol on the permeability of large unilamellar vesicles made by the extrusion technique (LUVET) (average diameter: about 250 nm), composed of dipalmitoyl or egg yolk phosphatidylcholines, were studied by monitoring the leakage of fluorescent dye, calcein, entrapped in the inner aqueous phase of the LUVET. The permeability was estimated from the apparent rate constant of calcein leakage at 25 degrees C. Large permeabilities were observed in the region of 0.6 M to 1.3 M ethanol, with a concentration dependence. In this range of ethanol concentrations the normal bilayer and interdigitated structure coexist and the membrane is in a phase-separated state. The large permeability is due to the instability of the boundary regions, the interdigitated membrane being characterized by a thinner structure and more rigid hydrocarbon regions in the layer than its non-interdigitated counter part. These results suggest the possibility of biomembrane-permeability regulation by interdigitated membrane formation.

Ethanol↗
PubMed1980

Ionic permeabilities of the frog perineurium.

Ionic permeation was investigated across the perineurium of the frog sciatic nerve, under normal conditions and following treatment by hypertonic Ringer, ouabain or amiloride. A cylindrical segment of perineurium removed from the nerve and mounted in vitro on two cannulae was continuously perfused. Permeation rates of 22Na and 42K across the perineurium were the same in either direction and were unaffected by the drugs. The mean 22Na permeability coefficient at the perineurium equaled 1.68 +/- 0.08 (S.E.M.) X 10(-6) cm/sec. Simultaneous measurement of transperineurial fluxes of 22Na, 42K and 36Cl indicated that the K/Na permeability ratio exceeded the ratio of limiting conductances of these ions in free solution, but that the Cl/K permeability ratio did not differ from the respective limiting conductance ratio. Immersion of the perineurial cylinder in Ringer, made hypertonic by addition of NaCl, increased the absolute permeability coefficients of the three ionic tracers but did not affect their permeability ratios. The flux ratio of 22Na/[14C]sucrose, however, was decreased by hypertonic treatment. It is concluded that there is no evidence of active Na or K transport across the perineurium and that the paracellular path in the perineurium exhibits size-dependent permselectivity properties. In addition, the low rates of transperineurial permeation of ions and water-soluble non-electrolytes (e.g. sucrose) are comparable to those in epithelia with tight junctions. These permeability coefficients provide quantitative estimates of the diffusion barrier properties of the perineurium.

Animals↗
PubMed1989

Perineurial permeability and endoneurial edema during Wallerian degeneration of the frog peripheral nerve.

Perineurial permeabilities to [3H]sucrose and [14C]dextran (MW = 70,000), and water content, conduction velocity (CV) and maximum amplitude (MAP) of the compound action potential, were determined in Wallerian degenerated nerves (sciatic or tibial) of the frog and compared with values in the contralateral uncut nerves. Three days after transection of the lumbosacral plexuses, about 2 cm proximal to the sciatic nerve, mean water content of the sciatic nerve was significantly higher than in the contralateral uncut nerve. After 10 days, the degenerating sciatic nerve showed significant increases in the mean perineurial permeabilities to [3H]sucrose and [14C]dextran when compared to values in the contralateral nerve. Means MAP's and CV's were significantly decreased. At 21 days and after, no compound action potential was detected and perineurial permeability and nerve water content had increased further. Decreases in mean MAP's and CV's and permeability increases of the perineurium were less in degenerating tibial nerves than in degenerating sciatic nerves. It is concluded that following transection, (1) Wallerian degeneration produces an irreversible increase in perineurial permeability, (2) the increase of perineurial permeability follows a proximodistal gradient, and (3) the frog peripheral nerve develops endoneurial edema during Wallerian degeneration as do degenerated nerves of mammals.

Action Potentials↗
PubMed1994

Intracarotid infusion of bradykinin selectively increases blood-tumor permeability in 9L and C6 brain tumors.

This study investigated the effects of bradykinin on blood-tumor barrier (BTB) permeability in transplanted 9L gliosarcomas (9L) and C6 gliomas (C6) in rats. Permeability, expressed as the unidirectional transfer constant, Ki (microliter/g/min), was measured by quantitative autoradiography. Tracers used to examined permeability included radiolabeled alpha-aminoisobutyric acid ([14C]AIB), sucrose ([14C]sucrose) and dextran ([14C]dextran). Intracarotid infusion of bradykinin (10 mg/kg/min) significantly increased the BTB permeability in both 9L and C6 tumors to [14C]AIB and [14C]sucrose, but did not increase permeability to [14C]dextran. Blood-brain barrier (BBB) permeability in normal (non-tumor) brain was not significantly increased to any of the tracers by intracarotid bradykinin infusion. Ki values for [14C]AIB, [14C]sucrose and [14C]dextran of 9L tumors in the bradykinin group versus control group were 41.6 +/- 12.6 vs. 24.8 +/- 6.30 (P < 0.02), 17.5 +/- 9.34 vs. 9.05 +/- 4.36 (P < 0.05), and 3.90 +/- 2.59 vs. 2.42 +/- 1.76, respectively (mean +/- S.D.). Ki values to [14C]AIB, [14C]sucrose and [14C]dextran of C6 tumors in the bradykinin group versus control group were 41.4 +/- 19.0 vs. 19.5 +/- 11.4 (P < 0.01), 18.0 +/- 8.88 vs. 7.06 +/- 3.05 (P < 0.01), and 4.07 +/- 1.45 vs. 2.27 +/- 1.26, respectively (mean +/- S.D.). Intracarotid infusion of bradykinin did not significantly increase the blood volume in tumor or brain tissue despite its known vasodilative effect. Intracarotid infusion of bradykinin may be a useful technique for selective delivery of compounds to brain tumors.

Aminoisobutyric Acids↗
PubMed1979

Effect of alpha-tocopherol incorporation of glucose permeability and phase transition of lecithin liposomes.

Liposomes were prepared from dipalmitoyllecithin, dimyristoyllecithin, dioleoyllecithin, egg lecithin, and soybean lecithin, and the effects of incorporation of various quantities of alpha-tocopherol or its analogs on permeability of the liposomes to glucose were studied at various temperatures (4--40 degrees C). Results showed that increase in the quantity of alpha-tocopherol incorporated into dipalmitoyllecithin and dimyristoyllecithin liposomes lowered the transition temperature for marked release of glucose and also decreased the maximum rate of temperature-dependent permeability, alpha-Tocopherol also had similar but less marked effects on the permeability of dioleoyllecithin and egg lecithin liposomes, but little effect on those of soybean lecithin, which has a higher degree of unsaturation. In dipalmitoyllecithin liposomes phytol showed a similar effect of permeability to that of alpha-tocopherol, but phytanic acid caused a different pattern of temperature-dependent permeability. With analogs of alpha-tocopherol, the regulatory effect on permeability decreased with shortening and disappearance of the isoprenoid side chain. The significance of these observations is discussed in relation to the physiological functions of tocopherols in natural membranes.

Glucose↗
PubMedDate not supplied

Permeability of lipid bilayers to water and ionic solutes.

The lipid bilayer moiety of biological membranes is considered to be the primary barrier to free diffusion of water and solutes. This conclusion arises from observations of lipid bilayer model membrane systems, which are generally less permeable than biological membranes. However, the nature of the permeability barrier remains unclear, particularly with respect to ionic solutes. For instance, anion permeability is significantly greater than cation permeability, and permeability to proton-hydroxide is orders of magnitude greater than to other monovalent inorganic ions. In this review, we first consider bilayer permeability to water and discuss proposed permeation mechanisms which involve transient defects arising from thermal fluctuations. We next consider whether such defects can account for ion permeation, including proton-hydroxide flux. We conclude that at least two varieties of transient defects are required to explain permeation of water and ionic solutes.

Diffusion↗
PubMed1985

Pharmacological analysis of the vascular permeability response in the anaphylactic phase of allergic inflammation in rats.

Allergic inflammation was induced by injecting an antigen (azobenzenearsonate-conjugated acetyl bovine serum albumin) solution into a preformed air pouch in the dorsum of sensitized rats. There was a marked increase of vascular permeability during the first 30 min, i.e. the anaphylactic phase, after the antigenic challenge injection. In an attempt to define the mediators responsible for the vascular permeability increase, series of experiments were performed with the aid of various pharmacologic agents. The combined treatment with pyrilamine and methysergide almost completely suppressed the anaphylactic vascular permeability response. However, FPL 55712, a specific antagonist to leukotrienes C4 and D4, components of slow-reacting substance, exerted no effect at doses sufficient to suppress the leukotriene C4-or leukotriene D4-induced vascular permeability increase. Indomethacin treatment was also ineffective. These results suggest that the anaphylactic increase in vascular permeability was mediated primarily by histamine and serotonin, while slow-reacting substance or prostaglandins did not play any significant role. A potent anti-inflammatory steroid, dexamethasone, exerted a dose-dependent inhibitory effect on the anaphylactic increase in vascular permeability without interfering with the liberation of histamine from mast cells. The mechanism of the steroid action is discussed.

Anaphylaxis↗
PubMed1983

The role of divalent cations in controlling amphibian lens membrane permeability; the mechanisms of toxic cataracts.

The effects of a range of divalent ions on lens sodium and potassium permeability characteristics were studied in calcium competition and replacement experiments. Resting voltage and conductance were measured and also voltage-independent conductance. Strontium and manganese were the only divalent ions able to maintain, in the absence of calcium, both sodium and potassium permeability at or near the control level. Neither cobalt nor magnesium had any effect on lens voltage of conductance in the presence of calcium, but neither of these ions could maintain lens permeability properties in the absence of calcium. Cadmium and barium had little effect on sodium permeability, but the former increased potassium permeability while the latter reduced it. Barium was the only divalent studied that appeared to inactivate voltage-sensitive potassium channels in the presence of calcium. Nickel, zinc and copper increased both sodium and potassium permeability in the presence of calcium and so they are likely to be particularly damaging to the lens. Copper was extremely toxic since it was able to overturn the regulatory influence of calcium when it was present in concentrations as low as 10(-6)M.

Animals↗
PubMed1992

Rabbit gut permeability in response to histamine chloramines and chemotactic peptide.

Granulocyte-derived chlorinated amines and bacterial formyl peptides are thought to enhance epithelial permeability. In the current study, gut permeability to [51Cr]ethylenediaminetetraacetic acid (EDTA) was monitored in response to luminal formyl-methionyl-leucyl-phenylalanine (fMLP) and histamine monochloramine and dichloramine. Responses were determined in rabbits during states of basal and elevated permeability. Luminal fMLP had minimal effects of gut permeability in control and injured states. Histamine monochloramine or dichloramine enhanced epithelial permeability under basal conditions; this effect was exaggerated by a pre-existing injury. Both histamine monochloramine and dichloramine retained full histamine agonist properties, and a combination of antioxidant and antihistamine therapy was required to block this increase in gut permeability. Whereas histamine chloramines caused a dose-dependent cytotoxicity in rat-cultured enterocytes, marked histological changes to the mucosa were not evident, nor were mucosal glutathione levels depleted. As histamine chloramines retain the histaminergic and oxidizing potential of their precursors, they represent a unique form of inflammatory mediator, although their highly reactive nature precludes in vivo confirmation of their formation.

Animals↗
PubMed1983

Effects of external Mg2+ and Ca2+ on branchial osmotic water permeability and prolactin secretion in the teleost fish Sarotherodon mossambicus.

In Sarotherodon mossambicus prolactin cell activity is related to ambient Ca2+ levels, and prolactin has hypercalcemic activity in this species. To study whether prolactin has a direct action on calcium metabolism, or whether prolactin's relationship with calcium is indirect and connected with control of gill permeability, the effects of external Ca2+ and Mg2+ on prolactin secretion and gill permeability were compared. It appeared that high external Mg2+ was associated with reduced prolactin secretion, even though high Mg2+ resulted in a marked hypocalcemia. Exposure of fish to high Ca2+ levels led to hypercalcemia. Both high Mg2+ and high Ca2+ concentrations in the ambient water reduced the osmotic water permeability of the gills. These results represent further evidence that prolactin secretion in S. mossambicus may be affected by any external factor that interferes with branchial permeability. It is concluded that prolactin's main function in this species is connected with control of branchial permeability rather than calcium metabolism, although internal calcium may be implicated in permeability control.

Animals↗
PubMed1995

Soluble CD14 in serum mediates LPS-induced increase in permeability of bovine pulmonary arterial endothelial cell monolayers in vitro.

Lipopolysaccharide (LPS) is a mediator of septic shock and acute respiratory distress syndrome (ARDS), conditions which are characterized by high-permeability pulmonary edema. LPS increases endothelial permeability both directly and indirectly via the pro-inflammatory cytokines produced by monocytes and macrophages. We investigated the role of soluble CD14 in serum in the increased endothelial permeability induced by LPS. Bovine pulmonary artery endothelial cells were grown to confluence on a microporous filter and the 125I-albumin clearance rate across the monolayer was determined. Even a high concentration of LPS (1 microgram/ml) did not increase endothelial permeability under a serum-free condition. In the presence of more than 3% normal human serum, LPS increased endothelial permeability. The presence of neutralizing anti-CD14 monoclonal antibody eliminated the serum-dependent effect of LPS. The addition of recombinant sCD14 completely replaced the requirement for serum. LPS-binding protein (LBP) did not enhance the rsCD14-mediated LPS effect, and anti-LBP antibody did not attenuate the serum-dependent LPS effect. These findings suggest that sCD14 in serum mediates the permeability-increasing effect on LPS on endothelial cells but that LBP is not necessary for this effect.

Acute-Phase Proteins↗
PubMed1988

Selectivity of the endothelial monolayer: effects of increased permeability.

We investigated the mechanism of thrombin-induced increases in endothelial monolayer permeability by examining the effect of thrombin on the molecular sieving characteristics of the endothelial monolayer and comparing the responses of arterial- and venous-derived endothelial cell lines. Bovine pulmonary artery (BPA) and pulmonary vein (BPV) endothelial cells were similarly harvested and cultured. The endothelial cells were grown to confluence on gelatinized polycarbonate filters and the permeabilities to sucrose, albumin, and IgG were measured and corrected for effects of unstirred layers. The control permeabilities of BPA and BPV were similar with both monolayers, demonstrating selectivity to different sized tracer molecules. alpha-Thrombin (10(-6) M) increased the permeability of both BPA and BPV to albumin and sucrose. The permeability of BPA was increased to a greater extent than BPV, perhaps due to phenotypic differences. In both cell lines, the permeability increase was most pronounced for albumin, which by pore theory is best described by an increase in the radius of the small pore pathway for diffusion.

Animals↗
PubMed1983

Histamine- and acetylcholine-induced changes in the permeability of the blood-brain barrier of normotensive and spontaneously hypertensive rats.

Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats were given saline, histamine (1.25, 2.5 or 5.0 micrograms/kg) or acetylcholine (1.0 or 2.0 micrograms/kg). Both agents caused a dose-dependent decrease in blood pressure which was greater in the spontaneously hypertensive animals. The permeability of the blood brain-barrier was measured with 131I-labelled serum albumin (RISA) or with 99mTc-sodium pertechnetate (TcO4-). The lowest dose of histamine caused a decrease in permeability of the blood-brain barrier to serum albumin in normotensive rats and acetylcholine caused an increase. Only the largest dose of histamine increased the permeability of the blood-brain barrier to serum albumin in spontaneously hypertensive rats. All doses of histamine and acetylcholine increased the permeability of the blood-brain barrier to sodium per technetate in nomotensive rats and the two lower doses of histamine increased the permeability in spontaneously hypertensive animals. This provides another example of the dissociation of change in the systemic blood pressure and change in the permeability of the blood-brain barrier.

Acetylcholine↗
PubMed1975

Potentiation of bradykinin-induced vascular permeability increase by prostaglandin E2 and arachidonic acid in rabbit skin.

The activity of prostaglandins (PG) in producing vascular permeability was quantitated by dye extraction method in skin of anaesthetized rabbits. PGE1 and PGE2 (0.01-10 mug) produced increase in vascular permeability. Activity was approximately equal to that of histamine (Hist) and 1/20 of that of bradykinin (BK) on a weight basis. The activity of PGF1alpha and PGF2alpha was only 1/20 of that of PGE1 or PGE2. In spite of the relatively low potency of PGE1 and PGE2 in the rabbit, near threshold doses (0.1 or 1 mug) of PGE2 could potentiate permeability responses to bradykinin (0.1 mug) by 10 or 100-fold, respectively. Equivalent doses (0.1 or 1 mug) of histamine could not potentiate the bradykinin responses. Arachidonic acid (AA) at 1 mug, produced a 10-fold potentiation in the permeability response to bradykinin (0.1 mug). Pretreatment of the rabbits with indomethacin (20 mg/kg, i.p.) reduced the responses of BK (0.1 mug) + AA (1 mug) down to a similar magnitude of those seen with bradykinin alone. However, indomethacin did not block responses to either, BK alone, BK + PGE2, or BK + Hist. Various doses (1, 10, 100 and 300 mug) of arachidonic acid alone also produced increase in cutaneous vascular permeability, although its potency was only 1/3-1/8 of that of PGE2. This activity of arachidonic acid was attributed in part to its bioconversion to PGE2, since its activity was significantly reduced by the prostaglandin antagonist, diphloretin phosphate (DPP) (60 mg/kg, i.v.) and by indomethacin (20 mg/kg, i.p.), which blocks conversion of arachidonic acid to prostaglandins. Arachidonic acid may owe some of its permeability increasing effects to histamine release, since its effects were also reduced by the anti-histamine, pyrilamine (2.5 mg/kg, i.v.).

Animals↗
PubMed1986

Tissue differences in vascular permeability induced by leukotriene B4 and prostaglandin E2 in the rat.

The activity of synthetic LTB4 and PGE2, in increasing vascular permeability was tested simultaneously in seventeen different organs in the rat. Rats were injected in the aortic arch through a cannula in the carotid artery with 125I-albumin, 51Cr-erythrocytes, and 57Co-EDTA. The rats were then injected through the carotid artery cannula with LTB4, PGE2 or a combination of LTB4 and PGE2. Eight minutes later the rats were killed and the activity of 125I, 51Cr, and 57Co measured in different organs. Changes in vascular permeability were inferred from changes in the ratios of the isotope activities. LTB4 (15 micrograms/kg) induced enhanced permeability in caecum, small bowel, skin, fat pad, stomach, pancreas, and aorta, but not in the heart, brain, colon, testes, diaphragm, forelimb, cremaster muscle, lung, kidney or eye. A lower dose of LTB4, 3 micrograms/kg, enhanced vascular permeability in caecum, small bowel, skin, stomach, and aorta. PGE2 (1 microgram/kg) enhanced vascular permeability only in the caecum. A combination of LTB4 (3 micrograms/kg) and PGE2 (1 microgram/kg) was more potent than either alone. Rats depleted of neutrophils with anti-neutrophil serum were less sensitive to LTB4 than intact rats. These findings suggest that the vasculatures of different tissues in the rat vary markedly in their susceptibility to LTB4 induced increases in permeability.

Animals↗
PubMed1993

Storage effects on dentin permeability and shear bond strengths.

The effects of duration of storage and selection of storage solution upon dentin permeability and bond strength were studied over a period of 8 days to 6 mon. Teeth were stored immediately after extraction in one of five commonly used solutions: 70% ethanol (E); 10% formalin (F); distilled water (W); distilled water with thymol (WT); or phosphate-buffered saline with thymol (ST). Permeability and lap shear bond strength measurements were evaluated in a repeated measures design (n = 20) after 8 days, 15 days and 6 mon. Dentin permeability varied with solution type and duration of storage as demonstrated by ANOVA, increasing F, E and the water-based solutions, respectively. Saline storage resulted in large significant decreases in permeability after prolonged storage, suggesting changes in dentin. Bond strengths were unaffected by duration of storage or by solution type, except for saline. Thus, permeability and bond strength values may be affected by storage conditions. The results of this study indicate that saline, the most commonly used solution in dental materials research, may be unsuitable for use as a result of its effect on dentin permeability and bond strength.

Analysis of Variance↗
PubMed1995

Influence of concentration and application time of maleic acid on dentin permeability.

OBJECTIVES: Since dentin permeability ultimately affects bond strength, the purpose of this study was to compare the effects of different concentrations of maleic acid, and different exposure times on dentin permeability. METHODS: One hundred and thirty freshly extracted human non-carious third molars were used. Hydraulic conductance was determined after various treatments. The teeth were divided into five groups. In the first group, the smear layer was untreated. In three other groups, 0.10, 0.25, or 0.5 M aqueous solution of maleic acid was applied on dentin slices for 15, 30, or 60 s. In the last group, the Scotchbond Multi-Purpose dental adhesive system (3M Dental Products) conditioner was applied for 15, 30, or 60 s. RESULTS: After a 60 s exposure time, the Scotchbond Multi-Purpose dentin conditioner or the 0.1 M solution of maleic acid was as effective at increasing dentin permeability as the 0.25 M and 0.5 M maleic acid solutions. The maximum dentin permeability was reached after 15 s with 0.25 M and 0.5 M solutions of maleic acid, after 30 s with Scotchbond Multi-Purpose and after 60 s with the 0.1 M solution of maleic acid. During the first 30 s, the 0.1 M solution of malic acid did not increase dentin permeability and did not completely remove the smear layer; a SEM examination of the dentin slices corroborated the functional results. SIGNIFICANCE: The manufacturer's recommendation of 15 s of etching using Scotchbond Multi-Purpose conditioning gel produced a moderate amount of etching which increases dentin permeability to about one-half its maximum value.

Acid Etching, Dental↗
PubMed1986

Plasmid genes increase membrane permeability in Escherichia coli.

The membrane permeability to o-nitrophenyl beta-D-galactoside is increased in the presence of rifampicin in Escherichia coli cells carrying srnB+ or pnd+ plasmids, but not in the cells carrying srnB- or pnd- mutant plasmids. The same permeability alteration was also observed at 42 degrees C when a rpoC4- mutant strain was used as a host strain in the absence of rifampicin. These results and the blockage of the effects by action of chloramphenicol suggest that the increase of permeability to o-nitrophenyl galactoside was caused by the expression of srnB+ or pnd+ gene, respectively. srnB+ gene expression leads to massive RNA degradation, probably through the activation of the rna+ gene product. In an rna- strain carrying the srnB+ plasmid, the extent of RNA degradation was reduced, whereas the permeability to o-nitrophenyl galactoside was increased to the same level as in the rna+ strain. Also, the increase in permeability to o-nitrophenyl galactoside was observed at 30 degrees C, although high-temperature incubation (42 degrees C) was necessary for the induction of RNA degradation. These results suggest that the alteration in permeability is a more direct effect of the expression of srnB+ or pnd+ gene and that the RNA degradation is a secondary phenomenon caused by the alteration in the membrane.

Bacterial Proteins↗