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J Randles

Publications and source records attributed to J Randles.

35 records · Page 2Linked to original sources
PubMed1979

Energetics of sugar transport by isolated intestinal epithelial cells: effects of cytochalasin B.

The capability of isolated intestinal epithelial cells to establish concentration gradients of 3-O-methylglucose (3-OMG) by a Na+-dependent transport system is limited by concomitant function of a Na+-independent, facilitated diffusion transport system. Monosaccharides accumulated by the active system are continuously lost via the passive system, which acts to lower steady-state sugar gradients maintained by the cell. Cytochalasin B is a potent inhibitor of the passive system and allows the cells to establish a sugar gradient that is much higher than normal. When extracellular [3-OMG] is 1 mM, cytochalasin induces sugar accumulation ratios of 30-fold (+/- phlorizin) in contrast to control ratios of approximately 10-fold. When [3-OMG] is 0.1 mM, cytochalasin (0.1 mM) induces 40-fold accumulation ratios. When changes in extracellular sugar concentration are considered, steady-state concentration gradients observed are 70-fold. For a Na:sugar coupling stoichiometry of 1:1, gradients of this magnitude represent the approximate theoretical maximum for a transport system driven exclusively by the transmembrane electrochemical potential for Na+.

Animals↗
PubMed1978

Effects of phloretin and theophylline on 3-O-methylglucose transport by intestinal epithelial cells.

Phloretin and theophylline each exert an immediate inhibitory effect on the Na+-independent, facilitated-diffusion transport system for sugar associated with intestinal epithelial cells. Phloretin inhibits approximately 50% more of the total Na+-independent sugar flux than theophylline. Neither agent has an immediate effect on the Na+-dependent, concentrative sugar transport system, although preincubation of the cells with phloretin causes a significant inhibition. The slowly developing effect is correlated with a decrease in cellular adenosine triphosphate (ATP) and an elevation of intracellular Na+. Other agents which elevate cell Na+ also inhibit Na+-dependent sugar influx, even if ATP levels are not depleted. On the other hand, if ATP is depleted by phloretin under conditions in which the cells do not gain Na+, the inhibitory effect on Na+-dependent sugar flux tends to disappear. The slow-onset phloretin effects are due to transinhibition of the Na+-dependent sugar carrier by cellular Na+. When the passive sugar carrier is inhibited by phloretin or theophylline, the concentrative system can establish an enhanced sugar gradient. Because of the secondary metabolic effects of phloretin, theophylline induces a greater gradient enhancement despite its more limited effect on the passive sugar-transport system. Sugar gradients as large as 20-fold are induced by theophylline, in contrast to 12-fold gradients observed in the presence of phloretin and approximately 7- to 8-fold for untreated cells. These results are discussed in terms of conceptual questions regarding the energetics of Na+-dependent transport systems.

Adenosine Triphosphate↗
PubMed1978

Phloretin-like action of bioflavonoids on sugar accumulation capability of isolated intestinal cells.

Flavanones and flavones are structural analogues of phloretin. Like phloretin they inhibit the non-Na+-dependent, facilitated diffusion transport system for sugars associated with the lateral serosal boundary of intestinal epithelial cells. The degree of inhibition varies with the extent and position of hydroxylation of the flavonoid nucleus. Flavones are more potent than corresponding flavanones. Tri- and tetrahydroxylated forms are more inhibitory than similar penta- and hexahydroxylated molecules. With one exception, none of the 18 flavonoids tested has secondary effects as metabolic inhibitors, as does phloretin. Inhibition of the passive sugar transport system with flavonoids allows the concentrative Na+-dependent sugar transport system to establish a better concentration gradient than is observed in untreated cells. The degree of gradient enhancement is proportional to the degree of inhibition of the sugar "leak." The flavonoid glycosides, which can be considered as phlorizin analogues, also inhibit the non-Na+-dependent sugar carrier, but less well than corresponding nonglycosylated agents. Only one of the glycosides inhibits the Na+-dependent transport system, and much less potently than phlorizin.

Animals↗
PubMed1977

Energetics of Na+-dependent sugar transport by isolated intestinal cells: evidence for a major role for membrane potentials.

Intestinal epithelial cells isolated from 6-wk-old chickens maintain the capability for Na+-dependent concentrative accumulation of 3-O-methylglucose (3-OMG). Cells depleted of ATP exhibit a transient accumulation of 3-OMG in response to imposed Na+ gradients ([Na+]o greater than [Na+]i) or when transmembrane ion diffusion potentials (cell interior negative) are established. Phlorizin or lack of extracellular Na+ prevents formation of sugar gradients in every case. A nonconcentrative, non-Na+-dependent sugar transport system is also operative in these cells. The latter system is inhibited to various degrees by phloretin, theophylline, cytochalasin B, and a variety of flavonones and flavones, including apigenin. These agents also act to inhibit efflux of sugar from the cell via this pathway. The concentrative system normally operates against a "leak" of sugar through the nonconcentrative carrier. If the passive system is made inoperative by any of the agents named above, a significant enhancement of steady-state sugar gradients maintained by the cells is observed. With cytochalasin B, gradients as large as 30-fold are established. The energy inherent in cellular Na+ gradients cannot account for sugar gradients of this magnitude unless both chemical electrical driving forces are considered. When the passive leak is maximmally inhibited, more than half of the total energy required must be derived from the membrane potential.

Animals↗
PubMed1976

2-Deoxyglucose transport by intestinal epithelial cells isolated from the chick.

Characteristics of 2-deoxyglucose uptake (2DG) by intestinal epithelial cells isolated from chickens were evaluated as a means of discriminating between the concentrative transport system for monosaccharides, associated with the mucosal brush border, and other possible routes of monosaccharide entry. 2DG was chosen as it is not a substrate for the mucosal transport system. The deoxysugar enters via a saturable pathway which is not Na+-dependent, is not inhibited by K+, does not accumulate solute against a concentration gradient; exhibits a high sensitivity to inhibition by phloretin; is relatively insensitive to phlorizin inhibition; and has low affinity [but high capacity relative to Na+-dependent mucosal transport of 3-O-methylglucose (3-OMG) and other monosaccharides]. These characteristics confirm those established in an earlier report for Na+-independent uptake of 3-OMG. Complications encountered in the use of 2DG as a test sugar include significant rates of metabolic conversion to an anionic form which presumably is a phosphorylated species. Methods for distinguishing between transport and subsequent metabolism are described. Inhibition of 2DG entry by several other sugars is described and inhibitory constants (K's) given for each.

Animals↗
PubMed1975

A Na+-independent, phloretin-sensitive monosaccharide transport system in isolated intestinal epithelial cells.

A monosaccharide transport system in addition to the active Na+-dependent system characteristic of the brush border surface of vertebrate intestinal tissue has been identified in isolated chick intestinal epithelial cells. The newly described system differs in several characteristics from the Na+-dependent process, including function in the absence of Na+; a high sensitivity to phloretin, relative insensitivity to phlorizin; different substrate specificity; and a very high KT and Vmax. The system apparently functions only in a facilitated diffusion manner so that it serves to move monosaccharide across the cell membrane down its chemical gradient. An appreciable fraction of total sugar efflux occurs via the Na+-independent carrier from cells which have accumulated sugar to a steady state. Phloretin selectively blocks this efflux so that a normal steady-state sugar gradient of seven- to eightfold is transformed to a new steady-state gradient which is greater than 14-fold. Locus of the new system is tentatively ascribed to the serosal cell surface where it would serve for monosaccharide transfer between enterocyte and lamina propria of the villus.

Animals↗
PubMedDate not supplied

Inhibition of the serosal sugar carrier in isolated intestinal epithelial cells by saccharin.

Isolated intestinal cells accumulate certain monosaccharides via an Na+-dependent, active transport system localized in the brush-border membrane, and release sugar molecules at the basolateral boundary via a facilitated diffusion, passive system. Work described here indicates that sodium saccharin (25-130 mM) has little if any direct effect on the active transport system, but that the passive transport system is inhibited by saccharin. A short period of exposure (10-60 min) is required for expression of the effect, which is detectable at saccharin concentrations as low as 10 mM. At 100 mM-sodium saccharin, as much as 50% inhibition occurs. Saccharin also appears to act as a weak metabolic inhibitor. The basis of the 'non-specific' effect is not understood, but it can compromise the capacity of the epithelial cells to form sugar gradients. When a sugar is accumulated that satisfies both transport systems (for example 3-O-methylglucose) the effect of saccharin on the passive transport system is the predominant one, and the cells establish a higher sugar gradient than that observed in the absence of saccharin. The 'non-specific' metabolic effect is manifested as an inhibition of sugar gradient formation when sugars that satisfy only the active system (such as alpha-methylglucoside) are accumulated.

Animals↗
PubMedDate not supplied

An alternative to urinary conduit.

The author outlines the procedures involved in creating a Mitrofanoff pouch as an alternative to urinary conduit. Patients who have such a procedure must learn to alter their lifestyles and acquire skills such as self-catheterisation, but early results suggest that they find the procedure acceptable and preferable to other options.

Counseling↗