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P M Wiggins

Publications and source records attributed to P M Wiggins.

17 recordsLinked to original sources
PubMed1990

Role of water in some biological processes.

The state of intracellular water has been a matter of controversy for a long time for two reasons. First, experiments have often given conflicting results. Second, hitherto, there have been no plausible grounds for assuming that intracellular water should be significantly different from bulk water. A collective behavior of water molecules is suggested here as a thermodynamically inevitable mechanism for generation of appreciable zones of abnormal water. At a highly charged surface, water molecules move together, generating a zone of water perhaps 6 nm thick, which is weakly hydrogen bonded, fluid, and reactive and selectively accumulates small cations, multivalent anions, and hydrophobic solutes. At a hydrophobic surface, molecules move apart and local water becomes strongly bonded, inert, and viscous and accumulates large cations, univalent anions, and compatible solutes. Proteins and many other biopolymers have patchy surfaces which therefore induce, by the two mechanisms described, patchy interfacial water structures, which extended appreciable distances from the surface. The reason for many conflicting experimental results now becomes apparent. Average values of properties of water measured in gels, cells, or solutions of proteins are often not very different from the same properties of normal water, giving no indication that they are averages of extreme values. To detect the operation of this phenomenon, it is necessary to probe selectively a single abnormal population. Examples of such experiments are given. It is shown that this collective behavior of water molecules amounts to a considerable biological force, which can be equivalent to a pressure of 1,000 atm (1.013 x 10(5) kPa). It is suggested that cells selectively accumulate K+ ions and compatible solutes to avoid extremes of water structure in their aqueous compartments, but that cation pumps and other enzymes exploit the different solvent properties and reactivities of water to perform work of transport or synthesis.

Animals↗
PubMed1989

Localization of a nonintercalative DNA binding antitumour drug in mitochondria: relationship to multidrug resistance.

The bis-(n-butyl) quaternary salt of N,N'-bis-(6-quinolyl)terephthalamide (QBQ), a fluorescent antitumour compound in the phthalanilide series which is thought to bind to the minor groove of the DNA double helix, has been investigated with respect to its in vitro activity and subcellular localization. Cultured MCF-7 human breast carcinoma cells concentrated QBQ in mitochondria by a time-dependent process which was inhibited by the ionophore valinomycin, suggesting a possible mode of antitumour action of QBQ through mitochondrial poisoning. Growth of cultured P388 murine leukaemia cells was inhibited 50% in the presence of 0.52 microM QBQ and multidrug-resistant P388 sublines developed for resistance to actinomycin D, vincristine, Adriamycin and the phthalanilide NSC 38280 were cross-resistant to the drug. Cross-resistance was reduced in all lines by the presence of 11 microM verapamil, suggesting that a transport resistance mechanism operates on QBQ. The actinomycin D-resistant P388 cell line was found to be cross-resistant to the aromatic cations rhodamine 123, which binds to proteins, and ethidium and pyronin Y, which bind intercalatively to DNA. Thus mitochondrion-specific drugs with different macromolecular binding properties all appear to be excluded by multidrug-resistant cells.

Animals↗
PubMed1986

Diffusion of butyrate through pig colonic mucus in vitro.

Using a modified equilibrium dialysis cell the rate of diffusion of butyrate through pig colonic mucus has been compared with that through other gels and unstirred layers. Relative diffusion coefficients were calculated for each layer. Layers of 8% polyacrylamide, and of caecal, mid-colonic and terminal colonic mucus, had coefficients that were 50-60% of the apparent free diffusion coefficient for butyrate, determined using layers made up of Millipore filters alone. The apparent free diffusion coefficients for butyrate (layers of agarose or filters) were 70% of previously determined values in the literature. This discrepancy can be explained by elements of the experimental procedure. All mucus layers differed significantly from layers of 2% agarose and Millipore filters but were not significantly different from layers of 8% polyacrylamide or from each other. Diffusion coefficients for butyrate in the mucus samples correlated with water content and carbohydrate content but had no relationship to protein content. The rate of diffusion of butyrate in colonic mucus layers was significantly reduced when compared with unstirred layers (P less than 0.05). Whether this has an effect on the butyrate supply to colonocytes in vitro and whether mucus in colonic disease behaves differently are subjects for further investigation.

Animals↗
PubMed1985

Pig gastric mucus: a one-way barrier for H+.

Gastric mucus is thought to protect the underlying mucosal cells from mechanical hazards and back-diffusion of luminal H+. In health, a pH gradient exists across the mucus layer from the variable low pH of the lumen to a pH approaching neutrality at the epithelial cell surface. By current hypotheses this gradient is maintained by the combined effects of an unstirred layer, restricted or slowed diffusion of H+ in the mucus, and the epithelial cell secretion of bicarbonate, which is confined to the cell surface by the mucus layer. These mechanisms do not explain how H+ is secreted through mucus in the first place. Using a modified diffusion chamber we have shown that pig gastric mucus facilitates a low-efficiency Na+/H+ exchange--a property that helps to clarify some previously unexplained components of H+ secretion. When a solution containing Na+ was separated by a layer of fresh pig gastric mucus from a solution of similar pH containing a much lower concentration of sodium, the sodium-rich solution was electrically negative relative to the sodium-poor solution and its pH decreased significantly with time. A similar pH gradient developed when the barrier was a synthetic cation-exchange membrane, and one of opposite sign when it was an anion exchanger; no pH gradient developed across neutral barriers. It is suggested that similar electrical coupling of H+ diffusion to active Na+ transport might in vivo ensure that secreted H+ moves into the gastric lumen.

Animals↗
PubMed1976

Intracellular pH of frog sartorius muscle.

A weak base, morpholine, has been labelled with 3H and tested for its suitability as an indicator for intracellular pH, by distribution in the tissue water of frog sartorius muscle in the species Hyla litoria. Its pK'a at 20 degrees C in a solution of the same ionic strength as frog Ringer was found to be 8.45 +/- 0.02, which is in the range of maximal sensitivity. Morpholine equilibrated with the tissue in 17 h; it was shown that it was not bound to intracellular constituents, that it was not metabolised nor toxic in the concentrations used; it was therefore judged suitable as a pH indcator. Intracellular pH was then measured by distribution of morpholine (6.985 +/- 0.08), nicotine (6.915 +/- 0.03) and the weak acid 5,5'-dimethyl-2,4-oxazolidinedione (7.10 +/- 0.05) and the pH-sensitive microelectrodes (5.9, the equilibrium value). It was shown that the four significantly different values could not be reconciled in terms of experimental error, heterogeneity of intracellular pH, liquid junction potential differences, or binding of indicator molecules inside the fibre. They could, however, be reconciled if the fibre water had different structure and solvent properties from the extracellular water and all ions were distributed across the membrane as between two liquid phases containing different solvents. Then the H+ would be in equilibrium, as shown by the microelectrode measurement, but intracellular pH would be indeterminable and probably greater than 6.

Animals↗
PubMed1976

Nature of the union between sheep red blood cells and T lymphocytes.

Calcium ions acting as salt bridges between the receptor on T lymphocytes and the negatively charged sites on sheep red blood cells (SRBC) are probably involved in rosette formation. Evidence to support this hypothesis includes the results of manipulating the ionic concentration of Ca2+free incubation medium and rosette inhibition in the presence of EDTA. Optimal rosette formation occurred when NaCl was the supporting electrolyte and the ionic strength was 100-150 mM. Neither KCl, CaCl2, MgCl2 nor Na2SO4 were effective as supporting electrolytes. SRBC pretreated with neuraminidase showed improved rosette formation of lower ionic strength than control cells.

Animals↗
PubMed1973

Ionic partition between surface and bulk water in a silica gel. A biological model.

Distribution of the biologically important ions between two aqueous phases of different structure has been used as a model for ionic distribution in living tissue. When other sources of specificity had been eliminated or corrected for, surface-oriented water in a silica gel was found to have increased solvent power for water-structure-breaking ions and decreased solvent power for water-structure-making ions; and the relative solubility of an ion in the phase of enhanced structure increased regularly with the water-structure-breaking powers of the ion. The ionic selectivity was decreased in the presence of urea. The selectivity of the gel water for potassium relative to sodium increased to a maximum when the gel surface was partially ionized so that distribution of cations was not linked to distribution of anions, and then decreased as the surface changed from a hydrogen bonding to an ionic surface. It is pointed out that the distribution of ions across most living cell membranes is qualitatively the same as that found in this silica gel, and it is suggested that the membrane separates two aqueous phases of different structure, and that the enhanced structure of cell water contributes to the observed ionic distributions.

Cell Membrane Permeability↗
PubMedDate not supplied

The sodium pump: a ghost story.

Evidence that the sodium plus potassium activated adenosinetriphosphatase ((Na + K)-ATPase) is present and functions normally in a red blood cell ghost is summarised. The case is then argued that since ghost move neither sodium nor potassium against an electrochemical gradient, the (Na+ + K)-ATPase is not in itself sufficient to generate transmembrane gradients of sodium and potassium ions. If it is not sufficient in ghost, then it cannot be sufficient in intact cells, but most somehow work co-operatively with the cytoplasm. An alternative hypothesis to that of carrier-mediated transported is then proposed, and shown to be consistent with data on intact cells, membrane homogenates, ghosts, and membrane vesicles derived from bacteria.

Adenosine Triphosphate↗
PubMedDate not supplied

A simple universal mechanism of use and conservation of energy: its application to movements of ions and other materials across cell, mitochondrial and other membranes and to oxidative phosphorylation.

A single simple mechanism by which all cells might both use energy to drive active transport to all solutes and also conserve energy in the form of adenosinetriphosphate (ATP) is descirbed. The basic assumption is that injection of energy results in a conformational change of the membrane which both generates transient highly-ordered water structures on its inside surface and changes membrane permeability. Ordered water is propagated through the cell by means of cooperative interactions with proteins, so that during the ordered period intracellular water is incompatible with small cations which require strong primary hydration, but has enhanced affinity for water-structure-breaking solutes. In animal cells cytoplasmic water is ordered by the activity of the plasma-membrane-bound transport ATPases. In mitochondria and bacteria the state of ordered water is identified with the energised state, which can be generated either by passage of electrons down the electron chain, or by ATPase activity. The mechanism is shown to be consistent with the observed transport activities of mitochondria and bacteria, and also provides a simple direct explanation of oxidative phosphorylation.

Adenosine Triphosphate↗