Lipophilic Pathway Research Articles

Foliar Calcium Absorption by Tomato Plants: Comparing the Effects of Calcium Sources and Adjuvant Usage.

The deficiency of calcium (Ca) reduces the quality and shelf life of fruits. In this scenario, although foliar spraying of Ca2+ has been used, altogether with soil fertilization, as an alternative to prevent deficiencies, little is known regarding its absorption dynamics by plant leaves. Herein, in vivo microprobe X-ray fluorescence was employed aiming to monitor the foliar absorption of CaCl2, Ca-citrate complex, and Ca3(PO4)2 nanoparticles with and without using adjuvant. We also investigated whether Sr2+ can be employed as Ca2+ proxy in foliar absorption studies. Moreover, the impact of treatments on the cuticle structure was evaluated by scanning electron microscopy. For this study, 45-day-old tomato (Solanum lycopersicum L., cv. Micro-Tom) plants were used as a model species. After 100 h, the leaves absorbed 90, 18, and 4% of aqueous CaCl2, Ca-citrate, and Ca3(PO4)2 nanoparticles, respectively. The addition of adjuvant increased the absorption of Ca-citrate to 28%, decreased that of CaCl2 to 77%, and did not affect Ca3(PO4)2. CaCl2 displayed an exponential decay absorption profile with half-lives of 15 h and 5 h without and with adjuvant, respectively. Ca-citrate and Ca3(PO4)2 exhibited absorption profiles that were closer to a linear behavior. Sr2+ was a suitable Ca2+ tracer because of its similar absorption profiles. Furthermore, the use of adjuvant affected the epicuticular crystal structure. Our findings reveal that CaCl2 was the most efficient Ca2+ source. The effects caused by adjuvant suggest that CaCl2 and Ca-citrate were absorbed mostly through hydrophilic and lipophilic pathways.

Features of the Early Hydrocarbon Accumulation and Its Effects on the Late Accumulation in Sandstone Reservoir: A Case Study of the Eocene Dongying Depression, Bohai Bay Basin

Multi-stage hydrocarbon generation and accumulation are very common in petroliferous basins. Also, determination of hydrocarbon accumulation stages and each related diagenetic feature is important for understanding the distribution of current oil and gas resources in one individual basin. However, in the case of conventional sandstone reservoirs, few studies have focused on these resulting reservoir features (e.g., physical property and wettability) that are caused by the first accumulation of hydrocarbons and their geological implications. In this study, taking the reservoir from the Eocene Dongying Depression as an example, we investigated the features of the early hydrocarbon accumulation and its effects on the late accumulation, by analyzing the early accumulation-related paragenesis, fluid inclusions, clay minerals content, reservoir physical property, and wettability in sandstones. Our results show that the early stage accumulation of the overpressured hydrocarbon fluid could support and offset some loads of overburden, weaken the normal compaction, and preserve some original pores. Also, the early hydrocarbon accumulation resulted in an alternated, diagenetic fluid environment from the initial acidic to subsequent alkalic conditions, with the overall dissolution intensity stronger than the cementation, and formed a large number of secondary pores. As a result, the early accumulation was beneficial to reservoir space development and provided more space for the late hydrocarbons. In addition, the early hydrocarbon accumulation could cause the alteration of rock wettability and gradually formed a lipophilic migration pathway from the source rock to the reservoir. Also, the late stage of hydrocarbons would preferentially choose this dominant pathway for their migration (i.e., inheritance of migration pathway).

Nanocarriers Call the Last Shot in the Treatment of Brain Cancers.

Our brain is protected by physio-biological barriers. The blood–brain barrier (BBB) main mechanism of protection relates to the abundance of tight junctions (TJs) and efflux pumps. Although BBB is crucial for healthy brain protection against toxins, it also leads to failure in a devastating disease like brain cancer. Recently, nanocarriers have been shown to pass through the BBB and improve patients’ survival rates, thus becoming promising treatment strategies. Among nanocarriers, inorganic nanocarriers, solid lipid nanoparticles, liposomes, polymers, micelles, and dendrimers have reached clinical trials after delivering promising results in preclinical investigations. The size of these nanocarriers is between 10 and 1000 nm and is modified by surface attachment of proteins, peptides, antibodies, or surfactants. Multiple research groups have reported transcellular entrance as the main mechanism allowing for these nanocarriers to cross BBB. Transport proteins and transcellular lipophilic pathways exist in BBB for small and lipophilic molecules. Nanocarriers cannot enter via the paracellular route, which is limited to water-soluble agents due to the TJs and their small pore size. There are currently several nanocarriers in clinical trials for the treatment of brain cancer. This article reviews challenges as well as fitting attributes of nanocarriers for brain tumor treatment in preclinical and clinical studies.

Coexistence of Lipid Phases Stabilizes Interstitial Water in the Outer Layer of Mammalian Skin

The lipid matrix in the outer layer of mammalian skin, the stratum corneum, has been previously investigated by multiple biophysical techniques aimed at identifying hydrophilic and lipophilic pathways of permeation. Although consensus is developing over the microscopic structure of the lipid matrix, no molecular-resolution model describes the permeability of all chemical species simultaneously. Using molecular dynamics simulations of a model mixture of skin lipids, the self-assembly of the lipid matrix lamellae has been studied. At higher humidity, the resulting lamellar phase is maintained by partitioning excess water into isolated droplets of controlled size and spatial distribution. The droplets may fuse together to form intralamellar water channels, thereby providing a pathway for the permeation of hydrophilic species. These results reconcile competing data on the outer skin’s structure and broaden the scope of molecular-based methods to improve the safety of topical products and to advance transdermal drug delivery.

On the correlation between single-frequency impedance measurements and human skin permeability to water

The objective of this study was to quantitatively compare measurements of tritiated water permeability with impedance determined at either 100 or 1000Hz using an LCR databridge on the same pieces of skin. A previously published expression based on a simple circuit of a parallel resistor and constant phase element (CPE) was used to relate (RPARA) measured at different frequencies to the DC resistance (RskinA) and the steady-state skin permeability of tritiated water (kp). Using this analysis, kp and (RPARA) data from three laboratories were shown to be consistent with each other, and kp and (RskinA) estimated from (RPARA) were linearly correlated. Compared with urea and mannitol, which are known to permeate skin through a polar pathway, the value of kp for water was found to be about two times larger than expected for transport through only the polar pathway, suggesting an approximately equal contribution from the lipophilic pathway. Equations relating kp to (RPARA) and (RskinA) were used to compare on a consistent basis proposed tests for identifying and excluding damaged skin from chemical absorption studies. The criterion of 20kΩcm2 for (RskinA) corresponds to a tritiated water permeability of 3.2×10−3cm/h, which should exclude damaged skin without screening undamaged but higher permeability skin samples from study.

Characterization of the diffusion of non-electrolytes across plant cuticles: properties of the lipophilic pathway

Systemic crop protection products are commonly sprayed onto foliage, whereupon the active substances must penetrate into the leaves in order to become biologically active. Penetration of the plant cuticle is the rate-limiting step. The diffusion of organic non-electrolytes within cuticles is a purely physical process that can be described and analysed in the same way as is done for diffusion in synthetic polymer membranes. Solute mobilities in cuticles vary considerably between plant species. For a given species they decrease with increasing solute size, and this size selectivity holds for all of the plant species investigated so far. Wax extraction from leaf cuticles increases the mobility of solutes tremendously, but size selectivity is not affected. Furthermore, diffusion within plant cuticles is extremely temperature dependent. An analogous increase in solute mobility can be achieved by using accelerators, which enhance the fluidity of the polymer matrix and of the waxes. The effects of temperature and plasticizers on the diffusion of non-electrolytes in wax and the cutin matrix have been used to characterize the nature of the lipophilic pathway. The 'free volume' theory can be used to explain the influence of the size and shape of the solute, and its dependence on temperature. The physico-chemical nature of the diffusion pathway has been shown, by thermodynamic analysis, to be identical for a wide range of solute lipophilicities. This approach also explains the mode of action and the intrinsic activity of plasticizers.

Towards complete cofactor arrangement in the 3.0 Å resolution structure of photosystem II

Oxygenic photosynthesis in plants, algae and cyanobacteria is initiated at photosystem II, a homodimeric multisubunit protein-cofactor complex embedded in the thylakoid membrane. Photosystem II captures sunlight and powers the unique photo-induced oxidation of water to atmospheric oxygen. Crystallographic investigations of cyanobacterial photosystem II have provided several medium-resolution structures (3.8 to 3.2 A) that explain the general arrangement of the protein matrix and cofactors, but do not give a full picture of the complex. Here we describe the most complete cyanobacterial photosystem II structure obtained so far, showing locations of and interactions between 20 protein subunits and 77 cofactors per monomer. Assignment of 11 beta-carotenes yields insights into electron and energy transfer and photo-protection mechanisms in the reaction centre and antenna subunits. The high number of 14 integrally bound lipids reflects the structural and functional importance of these molecules for flexibility within and assembly of photosystem II. A lipophilic pathway is proposed for the diffusion of secondary plastoquinone that transfers redox equivalents from photosystem II to the photosynthetic chain. The structure provides information about the Mn4Ca cluster, where oxidation of water takes place. Our study uncovers near-atomic details necessary to understand the processes that convert light to chemical energy.

Characterization of hydrophilic and lipophilic pathways of Hedera helix L. cuticular membranes: permeation of water and uncharged organic compounds

The permeability of astomatous leaf cuticular membranes of Hedera helix L. was measured for uncharged hydrophilic (octanol/water partition coefficient log K(O/W) < or =0) and lipophilic compounds (log K(O/W) >0). The set of compounds included lipophilic plant protection agents, hydrophilic carbohydrates, and the volatile compounds water and ethanol. Plotting the mobility of the model compounds versus the molar volume resulted in a clear differentiation between a lipophilic and a hydrophilic pathway. The size selectivity of the lipophilic pathway was described by the free volume theory. The pronounced tortuosity of the diffusional path was caused by cuticular waxes, leading to an increase in permeance for the lipophilic compounds after wax extraction. The size selectivity of the hydrophilic pathway was described by hindered diffusion in narrow pores of molecular dimensions. A distinct increase in size selectivity was observed for hydrophilic compounds with a molar volume higher than 110 cm3 mol(-1). Correspondingly, the size distribution of passable hydrophilic pathways was interpreted as a normal distribution with a mean pore radius of 0.3 nm and a standard deviation of 0.02 nm. The increased permeance of the hydrophilic compounds by the removal of cuticular waxes was attributed to an increase in the porosity, a decrease in the tortuosity, and a widening of the pore size distribution. Cuticular transpiration resulted from the permeation of water across the hydrophilic pathway. The far-reaching implications of two parallel pathways for the establishment of correlations between cuticular structure, chemistry, and function are discussed.

Accelerators Increase Permeability of Cuticles for the Lipophilic Solutes Metribuzin and Iprovalicarb but Not for Hydrophilic Methyl Glucose

Effects of diethylsuberate (DESU), tributyl phosphate (TBP), and monodisperse ethoxylated alcohols (EAs) on rate constants of penetration (k) of model solutes across astomatous cuticular membranes isolated from Madagascar ivy (Stephanotis floribunda) and pear (Pyrus communis) leaves were studied. Model solutes (selected on the basis of their octanol/water partition coefficients, K(ow)) were iprovalicarb (log K(ow) = 3.18), metribuzin (log K(ow) = 1.60), and methyl glucose (MG) (log K(ow) = -3.0). K(ow) varied by more than 6 orders of magnitude. Accelerators had wax/water partition coefficients (log K(ww)) ranging from 1.75 (DESU) to 4.32 (C(12)E(2)), and their equilibrium concentrations in Stephanotis wax varied from 0 to about 160 g kg(-)(1). Accelerators increase solute mobility in cuticles by increasing fluidity of cutin and waxes. This effect was quantified by plotting log k versus the accelerator concentration in wax. With the lipophilic solutes metribuzin and iprovalicarb, these plots were linear. Slopes of these plots characterize the intrinsic activities of the accelerators, and they decreased in the order DESU (0.029) > TBP (0.015) > EAs (0.01). Using these intrinsic activities, the effects of accelerators on rate constants of penetration can be calculated for any accelerator concentration in wax. For instance, at 50 g kg(-)(1), rate constants for lipophilic solutes increased by factors of 28 (DESU), 5.6 (TBP), and 3.2 (C(12)E(n)()), respectively. Permeability of cuticles for the hydrophilic MG was not increased by DESU, TBP, C(12)E(2), and C(12)E(4), while C(12)E(6) and C(12)E(8) increased it. Small hydrophilic solutes such as MG can access aqueous pores in cuticles, and this pathway is not affected by changes in fluidity of amorphous waxes. After rate constants of penetration of ionic CaCl(2) were compared with those for nonionic MG, it was concluded that 60% of the MG diffused across aqueous pores, while 40% used an alternative pathway. Because the solubility of MG in wax is extremely low, it is unlikely that MG diffused along the lipophilic pathway used by metribuzin and iprovalicarb. This agrees with the observation that DESU and TBP had no effect on rate constants for MG. An alternative pathway of unknown properties is suggested. It is speculated that C(12)E(6) and C(12)E(8) sorbed in cuticles might have generated a polar pathway for MG.

Size selectivity of aqueous pores in stomatous cuticles of Vicia faba leaves

Size selectivity of aqueous pores in Vicia leaf cuticles was investigated by measuring the penetration of calcium salts into the abaxial surface of detached leaves. Molecular weights of salts ranged from 111 g mol(-1) to 755 g mol(-1). Penetration in light at 20 degrees C and 100% humidity was a first order process and rate constants of penetration ranged from 0.39 h(-1) (CaCl2) to 0.058 h(-1) (Ca-lactobionate). Penetration was a first order process in the dark as well, but the rate constants were smaller by a factor of 1.82. Plotting logarithmatised rate constants versus anhydrous molecular weights resulted in straight lines both in light and in the dark. The slopes per hour were very similar and the average slope was -1.2 x 10(-3) mol g(-1). Hence, size selectivity was not affected by stomatal opening, and in light or darkness permeability of Vicia cuticles decreased by a factor of 2.9 when molecular weight increased from 100 g mol(-1) to 500 g mol(-1). Silver nitrate was preferentially precipitated as silver chloride in guard cells, glandular trichomes and at the base of trichomes. It was concluded that these precipitates mark the location of aqueous pores in Vicia leaf cuticles. The size selectivity of aqueous pores in Vicia leaf cuticles is small compared to that observed in poplar leaf cuticles, in which permeability decreased by a factor of 7-13 for the same range of molecular weights. It is also much smaller than size selectivity of the lipophilic pathway in cuticles. These findings suggest that active ingredients of pesticides, growth regulators and chemical inducers with high molecular weights penetrate leaves at higher rates when formulated as ions.

Size selectivity of aqueous pores in astomatous cuticular membranes isolated from Populus canescens (Aiton) Sm. leaves.

Little is known about the permeability of plant cuticles to ionic molecules with hydration shells that render them lipid insoluble and limit their diffusion to narrow aqueous pores. Therefore, the permeation of cuticular membranes to ionised calcium salts with anhydrous molecular weights ranging from 111 to 755 g mol(-1) was studied. Penetration was a first-order process and rate constants (k) (proportional to permeability) decreased exponentially with molecular weight. Plots of log k vs. molecular weight had slopes of -2.11x10(-3) and -2.80x10(-3), respectively, depending on the year in which the cuticular membranes were isolated. This corresponds to decreases in permeability by factors of about 7 to 13 when molecular weight increased from 100 to 500 g mol(-1). This size selectivity is small compared to the dependence on molecular weight of solute mobility in Populus cuticles. A decrease in mobility of neutral molecules by more than 3 orders of magnitude has been reported [A. Buchholz et al. (1998) Planta 206:322-328] for the same range of molecular weights. Hence, discrimination of large ionic species diffusing in aqueous pores (polar pathway) is much smaller than that for neutral solutes diffusing in cutin and waxes (lipophilic pathway). This indicates that formulating large solutes as ionic species would be advantageous.

Thermodynamic analysis of diffusion of non-electrolytes across plant cuticles in the presence and absence of the plasticiser tributyl phosphate.

Solute mobility in cuticular membranes (CMs) of 14 plant species (Citrus aurantiumn L., Citrus grandis L., Hedera helix L., Ilex aquifolium L., Ilex paraguariensis St.-Hil., Malus domestica Borkh. cv. Golden Delicious, Populus alba L., Prunus laurocerasus L., Pyrus communis L. cv. Bartlett, Conference and Gellerts Butterbirne, Pyrus pyrifolia (Burm. f.) Nakai, Schefflera actinophylla (Endl.) Harms and Strophanthus gratus Baill.) was measured over the temperature range 25-55 degrees C. The five organic model compounds differed in size (130-349 cm3 mol(-1)) and cuticle/water partition coefficient (18-10(8)). For all individual CMs (n = 297), the data were plotted according to the thermodynamic relationship between the preexponential factor (which is proportional to entropy) of the Arrhenius equation and the activation energy (enthalpy) of diffusion (ED). A strict linear correlation was obtained, providing evidence that the five compounds diffused along the same lipophilic diffusion path in all plant species tested. Extracting cuticular waxes from CMs of four plant species (Hedera, Pyrus, Schefflera and Strophanthus) had no effect on the slope of the plot but a parallel displacement towards higher entropy was observed with these polymer matrix (MX) membranes. This displacement is interpreted as a temperature-independent tortuosity factor directly related to entropy. The influence of the plasticiser tributyl phosphate on solute mobility at various temperatures was measured for CM and MX membranes. The plasticiser increased solute mobility and ED was reduced drastically for both membrane types. This plasticiser effect was almost completely reversible, when tributyl phosphate was desorbed from the membranes. For both, plasticised CM and MX, the thermodynamic correlation exists whereby all data points lie on the same line. The data are used to characterise the lipophilic pathway across plant cuticles in terms of the free-volume theory.

Calcium chloride penetrates plant cuticles via aqueous pores.

Penetration of calcium chloride across astomatous cuticular membranes (CMs) isolated from leaves of Pyrus communis L. has been studied. Penetration was a first-order process when calcium chloride concentrations ranged from 2 gl(-1) to 10 gl(-1). Rate constants were increased 10-fold by adding wetting agents but they did not depend on temperature. The accelerators tributyl phosphate and diethyl sebacate had no effect on rates of penetration. Increasing humidity over the salt residue on the CMs from 50 to 90% increased rate constants by about 2-fold. Extracting cuticular waxes from pear leaf CMs increased rate constants by factors of 2 to 3, depending on humidity. Leaf CMs from Malus domestica Borkh., Populus aelha L., Stephanotis floribunda Brongn. and Schefflera actinophylla (Endl.) Harms were also permeable to CaCl2. Highest rate constants were observed with poplar CMs while Schefflera CMs exhibited the lowest permeability. By comparing these results with the well established transport properties of the lipophilic pathway it is concluded that calcium chloride hexahydrate penetrated cuticular membranes via aqueous pores.

PH, p Ka and dermal delivery

The effect of pH on the permeation of ibuprofen and lignocaine through human skin has been modelled using a modification to the equation derived by Potts and Guy, which is normally applied to unionized entities. The results show that permeation is related to the distribution coefficient. The physicochemical properties have been predicted ab initio using commercially available software and compared to literature values. The approach is successful and shows that there is significant permeation of the ionized drugs through a lipophilic pathway, possibly as a result of ion pairing. Since the aqueous solubility of the ionized material is significantly higher than the unionized, the maximum flux through the skin may occur at a pH where ionization is high. Optimum topical or transdermal formulations may not therefore be for the free acid or free base.

Lidocaine and ATPase Inhibitor Interaction with the Chloroplast Envelope

Photosynthetic capacity of isolated intact chloroplasts is known to be sensitive to K(+) fluxes across the chloroplast envelope. However, little is known about the system of chloroplast envelope proteins that regulate this K(+) movement. The research described in this report focused on characterizing some of the components of this transport system by examining inhibitor effects on chloroplast metabolism. Digitoxin, an inhibitor of membrane-bound Na(+)/K(+) ATPases, was found to reduce stromal K(+) at a range of external K(+) and inhibit photosynthesis. Scatchard plot analysis revealed a specific protein receptor site with a K(m) for digitoxin binding of 13 nanomolar. Studies suggested that the receptor site was on the interior of the envelope. The effect of a class of amine anesthetics that are known to be K(+) channel blockers on chloroplast metabolism was also studied. Under conditions that facilitate low stromal pH and concomitant photosynthetic inhibition, the anesthetic, lidocaine, was found to stimulate photosynthesis. This stimulation was associated with the maintenance of higher stromal K(+). Comparison of the effects on photosynthesis of lidocaine analogs which varied in lipophilicity suggested a lipophilic pathway for anesthetic action. The results of experiments with lidocaine and digitoxin were consistent with the hypothesis that a K(+) channel and a K(+)-pumping envelope ATPase contribute to overall K(+) flux across the chloroplast envelope. Under appropriate assay conditions, photosynthetic capacity of isolated chloroplasts was shown to be much affected by the activity of these putative envelope proteins.

Effects of procaine on intracellular pH and its regulation: measurements with pH-selective micro-electrodes in Retzius neurones of the leech.

The experiments were performed with double-barelled micro-electrodes in Retzius neurones of the leech in order to see if the tertiary amine local anesthetic procaine affects intracellular pH (pHi) and its regulation. Lasting about 20 min, exposures to procaine (3 mM) saline caused an intracellular alkalosis of about 0.2 pH units which gradually degradated; its removal initiated a fast decrease of pHi resulting in an acidosis, fron which the cells recovered. Detailed studies, involving CO2 or NH4+ acid loaded cells as well as inhibition of the pHi regulating exchange mechanism by various drugs or exposures to Na-free salines suggest, that neither the Na+ -H+, nor a probably Na+ -dependent HCO3-(-)Cl- exchange are affected by procaine. We propose a model for procaine action on pHi assuming that neutral procaine passes the membrane easily through lipophilic pathways. The degradation of alkalinity during procaine exposure hints on an entry of loaded procaine, some possible transport paths of which are discussed.

Transdermal delivery of tetrahydrocannabinol

The skin permeation behavior of a tetrahydrocannabinol (THC) is described for the first time. In the design of transdermal delivery systems, Δ 8-THC was chosen over Δ 9-THC due to the former's better stability and its lower psychotropic potency. Sk permeation kinetic parameters were established through rat and human skin in vitro. The rat skin was found to be about 13-fold more permeable to Δ 8-THC than the human skin. Autoradiographs showed that 24 h after application the drug was concentrated in the stratum corneum, in the upper epidermis, and around the hair follicles, indicating that THC penetrates the skin through the lipophilic pathways. A transdermal formulation containing oleic acid as a permeation enhancer was tested in rats. A serum level of about 50 ng/ml cross-reacting cannabinoids (THC + metabolites) was maintained for about 24 h, indicating a sustained delivery of THC to the bloodstream. The transdermal preparation presented in this study is designed for future clinical studies.

Intestinal Permeability

Intestinal mucosa has an absorptive function and acts also as a selective barrier against potential antigenic, toxic and carcinogenic substances. Intestinal permeability can be defined as the capacity of mucosal surface to be penetrate by specific substances through unmediated diffusion. There are two theories about molecular permeation routes: the first one hypothesizes a transcellular (through small pores), a paracellular (through big channels) and a lipophilic pathways; the second one gives a key role only to paracellular tight-junctions. In many diseases we can find changes in intestinal permeability evaluable by simple and non invasive tests, administering "per os" probe molecules. These substances cross the epithelium in different way and amount according to their physicochemical features and mucosal integrity; then they reach circulation and are eliminated in urines where they can be detected. The most frequently molecules used are mono/disaccharides, 51Cr-labelled ethylenediaminetetraacetate (51Cr-EDTA) and polyethylene glycol (PEG). This simple method has become more and more used for diagnostic and speculative aims. These intestinal permeability tests have a low specificity so they cannot be used for a definitive diagnosis of intestinal disease; nevertheless, the high sensitivity for intestinal mucosal damage could make them a necessary method to evaluate mucosal integrity after therapy, to select patients with a specific symptoms and to support, particularly in pediatric populations, more specific and invasive diagnostic tests.

Antipyrine and aminopyrine permeability of individually perfused frog capillaries.

The mechanisms of transport of water and solutes across both hydrophilic and lipophilic pathways in the capillary wall were investigated. Paired measurements of the osmotic reflection and solute permeability coefficients of a lipid soluble solute (antipyrine MW 188 or aminopyrine 231) and a hydrophilic solute (glucose 180) were made on individually perfused capillaries of frog mesentery at temperatures between 5 and 25 degrees C. Below 15 degrees C, the lipophilic pathway accounts for less than 10% of the flux of antipyrine across the capillary wall, whereas at 25 degrees C the lipophilic pathway accounts of 50% of the flux. These results conform to the hypothesis that water and both hydrophilic and lipophilic solutes share an extracellular pathway, but water and lipids cross the cell by entirely separate routes. Both the activation energy for antipyrine and aminopyrine diffusion in the lipophilic pathway (25.9 kcal/mol) and the estimated cell membrane-water partition coefficients of the solutes are similar to values found for mammalian erythrocytes. Lateral diffusion in the cell membranes would account for the lipophilic pathway permeability just as well as diffusion across the cell membranes.

Permeability of novikoff hepatoma cells to water and monohydric alcohols

The permeability coefficients of Novikoff hepatoma ascites cell membranes for tritiated water ( 3HHO) and for a homologous series of monohydric alcohols (methanol through hexanol) were deduced from linear diffusion coefficients by means of a series-parallel pathway model (Redwood et al. (1974) J. Gen. Physiol. 64, 706–729). Membrane permeability coefficients for 3HHO at 20, 30 and 37°C were (all X10 −5) 97, 125, and 163 cm · s −1, respectively, and were significantly smaller than the corresponding values for the alcohols tested. In the alcohol series, ethanol had the lowest permeability coefficient 198 · 10 −5 cm · s −1 at 20°C. The apparent activation energy for water permeation was 6.7 ± 1.9 S.E. kcal · mol −1. The apparent membrane diffusion coefficients for the alcohols were a complex function of molecular properties with less diffusional membrane resistance to the alcohols in the middle of the homologous series than would have been expected on the basis of oil-water partitioning or molar volume considerations. The conventional parallel aqueous lipophilic pathway model is not consistent with the present data which can be interpreted by consideration of parallel lipophilic pathways through the Novikoff hepatoma cell membrane.