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 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies from this laboratory on the mechanism of O-alkyl bond formation using a microsomal system from Tetrahymena pyriformis have shown that O-alkyl lipid synthesized from dihydroxyacetone phosphate has exchanged one hydrogen stereospecifically from the 1-sn position of the glycerol moiety. Indirect evidence suggested that acyldihydroxyacetone phosphate, an intermediate in )-alkyl lipid synthesis, is probably not the locus of the exchange. In the present study in was shown that stable acyldihydroxyacetone phosphate incubated in the presence of tritiated water and Tetrahymena microsomes does not become tritiated. When hexadecanol is added to the system O-alkyl lipid is produced which has incorporated one atom of hydrogen for each mole of hexadecanol at all time periods examined. Experiments in Ehrlich ascites tumor cells have shown that the hydrogen exchange also occurs in a mammalian system. The results indicate that the mechanism of O-alkyl lipid ether bond formation involves a hydrogen exchange and that this exchange occurs after the formation of acyldihydroxyacetone phosphate.
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PMID:The formation of tritiated O-alkyl lipid from acyldihydroxyacetone phosphate in the presence of tritiated water. 80 79

1. Drinking by dogs has been studied during and after running on a treadmill, and compared with the drinking produced by NaCl given by stomach tube or intravenously. 2. When water was offered with a delay of more than 5 min after the end of a run producing loss of 30-90 g water by panting, the drinking was similar to that produced by NaCl, assuming that loss of 100 g water produces the same increase in plasma sodium as 15 m-mole NaCl. It is thus possible to explain drinking with a delay after the run as due to loss of water. 3. When water was offered immediately after a run or during pauses in the running there was drinking which cannot be explained as due to loss of water. Although the immediate stimulus to drinking is small, it may cause repeated small drinks by which the evaporative loss of water during running is matched by water intake. 4. Water (10-20 ml./kg body wt.) given by stomach tube before the run reduced or abolished drinking during running. Doses of water sufficient to stop drinking did not cause an increase in urine volume. 5. From these results a figure is produced placing in order mechanisms which may contribute to the control of water balance.
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PMID:Drinking by dogs during and after running. 80 73

Since chlorpromazine hydrochloride [2-chloro-10-(3-dimethylaminopropyl)-phenothiazine hydrochloride] is commonly implicated in causing bile-secretory failure in man and is secreted into bile, we have studied the physicochemical interactions of the drug with the major components of bile in vitro. Chlorpromazine hydrochloride molecules are amphiphilic by virtue of possessing a polar tertiary amine group linked by a short paraffin chain to a tricyclic hydrophobic part. At pH values below the apparent pK (pK'a 7.4) the molecules are water-soluble cationic detergents. We show that bile salts in concentrations above their critical micellar concentrations are precipitated from solution by chlorpromazine hydrochloride as insoluble 1:1 salt complexes. In the case of mixed bile-salt/phosphatidylcholine micellar solutions, however, the degree of precipitation is inhibited by the phospholipid in proportion to its mole fraction. With increases in the concentration of chlorpromazine hydrochloride or bile salt, micellar solubilization of the precipitated complexes results. Sonicated dispersions of the negatively charged phospholipid phosphatidylserine were also precipitated, but dispersions of the zwitterionic phospholipid phosphatidylcholine were not. Chlorpromazine hydrochloride efficiently solubilized these membrane phospholipids as mixed micellar solutions when the drug:phospholipid molar ratio reached 4:1. Polarizing-microscopy and X-ray-diffraction studies revealed that the precipitated complexes were amorphous and potentiometric studies confirmed the presence of a salt bond. Some dissociation of the complex occurred in the case of the most polar bile salt (Ks 0.365). As canalicular bile-salt secretion determines much of bile-water flow, we propose that complexing and precipitation of bile salts by chlorpromazine hydrochloride and its metabolites may be physicochemically related to the reversible bile-secretory failure produced by this drug.
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PMID:A study of the physicochemical interactions between biliary lipids and chlorpromazine hydrochloride. Bile-salt precipitation as a mechanism of phenothiazine-induced bile secretory failure. 82 66

The permeability of the toad urinary bladder to 22 nonelectrolytes was obtained from measurements of radioactive tracer fluxes. The permeability coefficients (P's), after suitable corrections for unstirred layers, were proportional to the olive oil/water partition coefficients for the majority of the molecules (Palpha Koill.3). In the absence of chain branching, inductive effects, and intramolecular hydrogen bonding effects, a hydroxyl group reduced P an average 500-fold and a methylene group increased P an average four fold. Branched chain solutes were less permeable than their straight chain isomers, and small solutes, polar and nonpolar, exhibited higher rates of permeation than expected from the relationship between P and Koil. (Over the molecular size range 18-175 cc/mole Palpha(Molecular Volume)-2.7.) The high rates of permeation of small molecules are consistent with diffusion through a highly organized lipid structure. Large polar solutes, e.g., sucrose, appear to pass across the epithelium via an extracellular shunt pathway. The apparent activation energies (Ealpha) for the permeation of 16 select molecules were obtained from permeability measurements over the temperature range 2-32 degrees C. Linear Arrhenius plots (i.e., log P/T-1) were obtained for all molecules after unstirred layer corrections. In the absence of these corrections "phase transitions" were seen for molecules with very high P's (P greater than 300 X 10(-7) cm/sec), but these are simply due to diffusion limited permeation. Ealpha increased by 2.5-3.6 kcals/mole with the introduction of each additional methylene group into a molecule, and decreased by up to 9 kcals/mole for the addition of a hydroxyl group. Qualitatively similar results were obtained in preliminary studies of olive oil/water partition coefficients. Arrhenius plots of the toad bladder conductance over the temperature range 2-32 degrees C yield apparent activation energies of 4-5 kcals/mole which is identical to that found previously for "leaky" epithelia.
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PMID:Effect of temperature on nonelectrolyte permeation across the toad urinary bladder. 82 48

Quaternary salts of 4-picoline are shown to act as efficient quenchers of tryptophan fluorescence in membrane proteins. Fluorescence quenching determinations of sarcoplasmic reticulum membranes from rabbit muscle and of human erythrocyte membranes of different cholesterol to phospholipid mole ratios (C/PL) were carried out with quaternary picolinium salts in phosphate-buffered saline (PBS) and in 2,2,2-trifluorethanol (TFE)-water 2:1 (v/v), where the membrane is presumably completely disintegrated. In both solvent systems, the tryptophan quenching characteristics were typical of heterogenous systems and were analyzed as such. The ratio of the fraction of fluorescence intensity available for quenching with N-methylpicolinium perchlorate in PBS and in 2:1 TFE-water, (formula: see text), was taken as an index for the bulk degree of exposure of the membrane proteins to the aqueous surrounding. This value was found to increase with C/PL which is in line with the notion that increase in lipid microviscosity results in increase of exposure of membrane proteins. Analogous experiments were performed with N-hexyl- and N-benzylpicolinium, which can quench tryptophyl residues in both the aqueous phase and the hydrocarbon-water interface, and with N-hexadecylpicolinium which is dissolved in the membrane lipid layer and acts mostly as a static quencher of tryptophan at the hydrocarbon-water interface. With these quenchers the complementary indices (formula: see text) and (formula: see text), which represent the fraction of the protein mass located in the hydrocarbon-water interface and in the hydrocarbon layer, respectively, could be semiquantitatively resolved.
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PMID:Degree of exposure of membrane proteins determined by fluorescence quenching. 84 25

An analytical method for the measurement of quaternary ammonium compounds in biological fluids has been developed. Samples are prepared by forming the corresponding iodides, which are extracted and isolated. The residue is taken into n-hexane or into water and part of the solution obtained is injected onto the gas chromatograph where thermal degradation takes place. The methyl iodide released is measured by a 63Ni electron capture detector. This method is quite sensitive and detects with good reliability and reproducibility as little as 10(-14) mole quaternary ammonium compound.
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PMID:Simplified detection of quaternary ammonium compounds by gas chromatography. 85

1. With the aid of micropuncture techniques, proximal tubular transepithelial concentration differences for Na (deltaC Na) and chloride (deltaC Cl) were measured in kidney cortex slices at bathing fluid Na concentrations from 10 to 400 m-mole. kg-1. Tissue content of water, Na and K was also measured in such slices. Under steady-state conditions of zero net flux of NaCl and water, deltaC Na represents the sum of active Na transport, factored by the tubular permeability coefficient added to a component of flux due to electrical forces. 2. The relation between bathing fluid Na concentraton and deltaC Na appeared sigmoid in form suggesting an allosteric mechanism for the transport step. 3. Transtubular potential difference, calculated from transepithelial Cl distribution ratios, did not appear constant at the various bathing fluid Na concentrations. Correcting for the effect of these potential differences on the value of each deltaC Na did not convert the sigmoid transport curve to a hyperbolic one, confirming the suggested allosteric nature of the active Na transport step. 4. Intracellular Na content varied linearly with bathing fluid Na concentrations implying free entry of this cation into the cell. This also suggests that the sigmoid transport curve is related to the properties of the active Na transport pump.
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PMID:Trans-proximal tubular steady-state concentration differences studied by micro-puncture and tissue content of sodium and chloride at varying intraluminal sodium concentrations in vitro in rat kidney cortex slices: evidence for a multisite sodium transport system. 85 86

1. The mechanism of placental transport of Na was studied in guinea-pigs in placentae with intact umbilical blood circulation or in the preparation of the placenta perfused in situ. 2. A constant level of 22Na was maintained in maternal plasma for 60 min, and from the quantity of 22Na recovered from the foetus at the end of this period the influx of Na from mother to foetus was calculated. Ligation of the omphalomesenteric vessels (supplying the everted yolk sac with blood) had no effect on the influx, the corresponding values of influx in the control and treated foetuses being 0-235 +/- 0-020 and 0-247 +/- 0-029 micron-mole/min. g foetal weight (n = 6, the limits are S.E. of mean). The specific activity of Na in amniotic fluid was below that of the maternal or foetal plasma Na by two orders of magnitude. These observations indicate that the extraplacental transport of Na into the foetus is negligibly low. 3. The electrical potential difference (p.d.) and unidirectional fluxes of Na across the placenta perfused in situ were measured by means of 22Na and 24Na administered to the opposite sides of the placental barrier. The fluxes varied with the weight of the foetuses whose placentae were perfused. The flux from the maternal to the foetal side was 0-270 +/- 0-017 micronmole/min.g foetal weight, the flux from the foetal to the maternal side was 0-340 +/- 0-018 micronmole/min.g foetal weight (n = 38). The corresponding p.d. was - 20-7 +/- 1-2 mV (foetal side negative). 4. The active component of Na transport across the placenta was calculated from the unidirectional fluxes and the p.d. The active transport was directed from the foetal to the maternal side, and its rate was 0-211 +/- 0-015 micronmole/min.g foetal weight (n = 38). During perfusion of the placenta with KCN (10(-3) M) the active transport decreased by approximately one third. 5. The flux of Na from the foetal to the maternal side of the perfused placenta was higher than the flux from the maternal to the foetal side. A similar asymmetry of Na fluxes was observed in the non-perfused placenta, the flux from mother to foetus being 0-180 +/- 0-013 micronmole/min.g foetal weight and the flux from foetus to mother 0-235 +/- 0-024 micronmole/min.g foetal weight (n = 12). This indicates that the asymmetry of Na fluxes is caused by the anaesthesia and/or by the trauma of the operation rather than by the perfusion of the placenta. 6. The permeabilities of the perfused placenta to Na and sucrose measured simultaneously from the maternal to the foetal side were 0-0767 +/- 0-0183 and 0-324 +/- 0-0094 cm3/min (n = 7y, respectively. The permeability values bear the same relation to each other as the respective coefficients of free diffusion in water, suggesting that the passive transport of Na across the placenta takes place as simple diffusion through wide aqueous channels. 6...
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PMID:Placental transport of sodium in the guinea-pig. 85 87

The degradation kinetics of pentobarbital sodium in propylene glycol-based solutions were studied along with the in vivo effects in laboratory animals. The degradation rate constant was directly proportional to the water concentration in propylene glycol-water solvent systems. An activation energy of 23.4 kcal/mole was obtained in propylene glycol-water (1:1). Pentobarbital sodium solutions in anhydrous propylene glycol and 9:1 mixtures of propylene glycol with ethanol, glycerin, or dimethylacetamide gave relatively slow degradation rates at 100 degrees with all projected 25 degrees t 99% values greater than 4.5 years. Intravenous administration of pentobarbital sodium in various anhydrous propylene glycol-based vehicles to rats produced no hemolysis of gross organ damage that would interfere with pathological evaluations. Results of an intraperitoneal sleeptime study indicated that pentobarbital sodium produced consistent hypnotic effect when administered as an aqueous solution or in anhydrous propylene glycol-based vehicles.
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PMID:Stable nonaqueous pentobarbital sodium solutions for use in laboratory animals. 87 53

1. The entry of Li into the vascular smooth muscle cells of the rat tail artery follows first-order kinetics with a rate constant of approximately 1.3 hr(-1) at 10 mM-[Li](o). The rate constant decreases gradually to ca. 0.5 hr(-1) when the [Li](o)/[Na](o) ratio is increased.2. Replacement of Na with Li over the range of [Li](o) from 1 to 115 mM, accomplished at constant ionic strength and osmolarity of the bathing solution, produces changes in cell Na and K without apparent change in cell water. At equilibrium, cell Li increases in linear proportion to [Li](o), at a ratio of 2:1 throughout the range. The increase in cell Li is associated with inverse falls in both cell K and Na such that the ratio of cell K to cell Na remains constant at ca. 10:1 throughout.3. The changes in the ionic contents, induced by equilibration of the tissue with a Na-free, Li-substituted solution, are reversible.4. Replacement of Na with sucrose over the range of 40-115 mM results, at equilibrium, in a linear fall in cell Na without conspicuous change in cell K. A constant portion of the cell Na, ca. 10 m-mole/kg dry wt., does not participate in this exchange.5. At equilibrium, reductions in [Na](o) are reflected in corresponding reductions in apparent [Na](i) such that the [Na](o)/[Na](i) ratio remains constant.
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PMID:The effects of external sodium substitution on cell sodium and potassium in vascular smooth muscle. 91 71


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