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Papaverine reduces the sodium permeability of the apical membrane and the potassium permeability of the basolateral membrane in isolated frog skin.

The effect of papaverine, an inhibitor of the phosphodiesterase responsible for breakdown of cAMP, on the transepithelial sodium transport across the isolated frog skin was investigated. Serosal addition of papaverine caused initially an increase in the short-circuit current (SCC), a doubling of the cellular cAMP content and a depolarization of the intracellular potential under SCC conditions (Vscc). The initial increase in the SCC was followed by a pronounced decrease both in the SCC and in the natriferic action of antidiuretic hormone (ADH), but papaverine had no inhibitory effect on the ability of ADH to increase the cellular cAMP content. As SCC declines, no hyperpolarization was observed. The I/V relationship across the apical membrane during the inhibitory phase, revealed that papaverine reduces the sodium permeability of the apical membrane (PNaa) as well as intracellular sodium concentration. These observations and the previously noted effect of papaverine on Vscc indicates that papaverine must have an effect on the cellular Cl or K permeability. The basolateral Na,K,2Cl cotransporter was blocked with bumetanide, which should bring the cellular chloride in equilibrium. Bumetanide had no effect on basal SCC and Vscc. When papaverine was added to skins preincubated with bumetanide, the effect of papaverine on SCC and Vscc was unchanged. Therefore, the depolarization of Vscc, observed during the papaverine-induced inhibition of the SCC, must be due to a reduction in the cellular K permeability. In conclusion, it is suggested that papaverine reduces the sodium permeability of the apical membrane and the potassium permeability of the basolateral membrane of the frog skin epithelium.

Animals

Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). II. Application to normal and abnormal permeability states in man and animals.

A new approach to the measurement of intestinal permeability using low molecular weight polyethylene glycols (PEG 400) has been applied to the study of normal and abnormal permeability states in man and animals. Successful assessments of gastric, jejunal, ileal, and colonic permeability suggest that the technique has application to any area of the gastrointestinal tract. The method has shown that bile acids alter mucosal permeability in the stomach and colon and that celiac sprue is associated with decreased intestinal permeability. These examples illustrate the potential of the technique for studying the function of diseases intestine in man.

Adult

A protease-like permeability factor in the guinea pig skin. 2. In vitro activation of the latent form permeability factor by weakly acidic phosphate buffer.

Conditions for the in vitro activation of the latent form of a protease-like permeability factor in the pseudoglobulin fraction from guinea pig skin were examined. (1) The factor was activated by dialysis against 67 mM phosphate buffer at pH 5.8--6.4, not at pH 7.0--8.0. (2) High salt concentration (200 mM or greater phosphate buffer or 67 mM phosphate buffer containing 200 mM or greater KCl or NaCl) prevented the activation at pH 6.2. (3) High osmotic pressure (sucrose at 1 M) did not affect activation at pH 6.2. (4) Reconversion of the activated permeability factor into an inactive form was not observed under high salt conditions, under which the latent permeability factor was stable in its own form. (5) The molecular size of the latent permeability factor was estimated as approx. 80 000 by Sephadex G-100 gel filtration at high salt concentration.

Animals

Effect of propranolol on ricinoleic acid- and deoxycholic acid-induced changes of intestinal electrolyte movement and mucosal permeability. Evidence against the importance of altered permeability in the production of fluid and electrolyte accumulation.

Hydroxy fatty acids and bile acids produce both intestinal fluid and electrolyte accumulation and increases in inulin clearance, a parameter of mucosal permeability. The relationship of the changes in mucosal permeability to the production of fluid and electrolyte accumulation is uncertain. These experiments were designed to determine whether the alterations of mucosal permeability produced by ricinoleic acid and deoxycholic acid were related to production of hydroxy fatty acid- and bile acid-induced fluid and electrolyte accumulation in the rat colon. Propranolol (1 mg per 100 g of body weight) administered daily for 3 days inhibited ricinoleic acid- and deoxycholic acid-induced Na and water accumulation. In contrast, propranolol did not affect either the increase in inulin clearance or the decrease in electrical potential difference produced by ricinoleic acid and deoxycholic acid. Further, amphotericin B increased inulin clearance by the colon and also increased water and Na absorption. These studies suggest that changes in mucosal permeability are not primarily responsible for hydroxy fatty acid- and bile acid-induced fluid and Na accumulation.

Amphotericin B

[Permeability-increasing effect of punctates. 3. Inhibition of the permeability-increasing activity by contrykal].

The punctate of the pleural cavity of a patient was examined which very much increased the permeability of the membrane in the animal experiment. Proteases is ascribed the effect increasing permeability, which are adsorbed to macromolecules. The increase of permeability could be inhibited by contrycal. An increase of permeability by proteolytic enzymes is discussed as one of the possible pathomechanisms for the development of exudations.

Animals

Ion permeability and strength of cell contacts: ion permeability and mechanical properties of cell contacts in small intestine epithelium.

The effects of several simple parameters (pH, concentration of bivalent cations, osmotic pressure, and temperature) on the ion permeability and mechanical properties of cell contacts have been investigated. It has been shown that the mechanical properties of a cell contact make it possible to describe it as a viscoelastic system. The main contribution to cell adhesion is made by the tight junction. Two populations of acidic centers have been identified on the cell membrane surface. One population interacts with bivalent cations to assure cell adhesion. The other population of weaker acidic centers regulating ion permeation is involved in the cell membrane's interaction of the repulsion type. An intimate correlation has been established between changes in passive transepithelial ion permeability and cell adhesion in response to changes in pH and in bivalent cation concentration. Such a correlation is possible if the tight junction is the principal contributor to the passive ion permeability and mechanical strength of the cell contacts.

Animals

[Estimation of pulmonary vascular permeability by indocyanine green in permeability pulmonary edema].

In this study we attempted to estimate pulmonary vascular permeability by indocyanine green (ICG). Permeability pulmonary edema was produced in 9 adult dogs by injecting 0.08 ml/kg oleic acid. We injected 50 mg ICG intravenously in 18 dogs (9 dogs with pulmonary edema and 9 control dogs). We measured the time course of ICG concentrations in pulmonary arterial blood, ICG concentration of peripheral lung tissue, tissue/serum ICG concentration ratios, and wet/dry lung weight ratios. The following results were obtained. The time course of ICG concentration in pulmonary arterial blood showed peak values at 2 minutes and became constant at 5 or 10 minutes after injection. The ICG concentration in peripheral lung tissue, tissue/serum ICG concentration ratios, and wet/dry lung weight ratios in the pulmonary edema group were significantly higher than those in the normal group. There was a strong linear correlation between wet/dry lung weight ratio and ICG concentration in peripheral lung tissue, with correlation coefficients of r = 0.936 (p < 0.01) in the right lung and r = 0.901 (p < 0.01) in the left lung. From these results, we conclude that estimation of pulmonary vascular permeability by ICG is a useful method.

Animals

Permeability studies on taeniid metacestodes: II. Antibody-mediated effects on membrane permeability in larvae of Taenia taeniaeformis and Taenia crassiceps.

Incubation in immune rat serum (IRS) was shown to increase the rate of absorption of 125I RNase-A but not 125I BSA by larvae of Taenia taeniaeformis and T. crassiceps. This effect required a heat labile factor in serum, and partial activity could be restored in heat-treated IRS by adding normal rat serum (NRS) as a source of complement. In addition, the effectiveness of IRS in altering permeability was shown to be dependent on the concentration of functional complement. Both live and dead larvae incubated in NRS rapidly depleted hemolytic complement levels in the surrounding medium. Immunoglobulin fractions from IRS separated by anion exchange chromatography and and gel filtration were tested in the presence of excess complement for their ability to affect uptake of 125I RNase-A. Enhanced permeability was observed in larvae incubated in each fraction. The results show that antibodies in conjunction with complement are capable of disrupting larval permeability control in vitro. The observation that larvae were able to restore normal control as complement levels declined suggests that the parasites may overcome this immunologic effector mechanism by interfering with complement function.

Animals

Resistance to Pediococcus cerevisiae to amethopterin as a consequence of changes in enzymatic activity and cell permeability. II. Permeability changes to amethopterin and other folates in the drug-resistant mutant.

the accumulation of amethopterin in a Pediococcus cerevisiae strain resistant to this analogue was about 30% of that in P. cerevisiae/PteGlu, the sensitive parent. The uptake in the resistant strain was strictly glucose dependent, whereas in the sensitive parent about 16% accumulation occurred in absence of glucose. The transport in both strains was inhibited by iodoacetate and KF. Amethopterin uptake exhibited saturation kinetics with an apparent Km of 5 muM in P. cerevisiae/AMr and 0.5 muM in P. cerevisiae/PteGlu. The apparent V was 0.2 nmol per min per mg cells (dry weight); the same for both strains. The optimum pH for the uptake of amethopterin by P. cerevisiae/AMr and P. cerevisiae/PteGlu was pH 6.0. Folate and methyltetrahydrofolate competitivity inhibited amethopterin uptake with apparent Ki values of 8 and 0.7 muM, respectively. The uptake of folate exhibited a slightly increased Km value as compared to that of the sensitive strain, whereas the uptake activity velocity was in the same range. Methyltetrahydrofolate accumulated up to about 60-fold higher intracellular concentration than that of the medium, which is a markedly lower accumulation from that in the sensitive strain. The uptake was glucose dependent and inhibited by iodoacetate and KF. The pH optimum for methyltetrahydrofolate uptake in the resistant strain was the same as that in the sensitive parent (pH 5.7--6). In contrast to the increase in the apparent Km value for amethopterin in the resistant strain, the affinity of the carrier for methyltetrahydrofolate was apparently unchanged, whereas the V value was about 16 times lower than that in the sensitive strain. The Ki for amethopterin when added to increasing concentrations of methyltetrahydrofolate was 5.2 muM, a value about the same as that of the Km.

Biological Transport, Active