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P F Curran

Publications and source records attributed to P F Curran.

At least 19 recordsLinked to original sources
PubMed1977

Na and Cl transport and short-circuit current in rabbit ileum.

Na and Cl fluxes and short-circuit current (Isc) in rabbit ileum have been studied as a function of ionic concentrations in HCO3-free solutions. Both net Na flux (JNanet) and Isc show similar saturation functions of [Na] at fixed [Cl]. They show no significant difference between zero and 112 mM Na but at 140 mM Na Isc is significantly greater than the JNanet. Net Cl transport, secretion, is observed only at 140 mM Na and is approximately equivalent to the difference between the Isc and JNanet. The transcellular mucosa-to-serosa Na fluxes measured at 140 and 70 mM Na do not differ significantly from the corresponding Isc. The net Cl flux varies with [Cl] at fixed [Na] while Isc is virtually not affected by [Cl]. These results suggest that the absorptive Na transport process is electrogenic and responsible for the Isc and that the secretory fluxes of Na and Cl are coupled, require high [Na], vary with [Cl], and do not contribute to Isc. K-free solution abolishes the Isc after a prolonged lag. Finally, the effect of a low resistance shunt pathway on active Na absorption is examined with a four-compartment model.

Animals↗
PubMed1976

Mucosal and serosal fluxes of alanine in rabbit ileum.

The four unidirectional fluxes of alanine across the mucosal and serosal borders of rabbit ileum were evaluated as functions of the alanine concentration on a single piece of tissue using a method previously described (Naftalin, R.J. and Curran, P.F. (1974) J. Membrane Biol. 16, 257-278). The effects of Na+ removal and of ouabain on these fluxes were investigated. Alanine was actively transported across the mucosal membrane under control conditions; Na+ removal or ouabain inhibited this process as a result of a decrease in flux from the mucosal solution to the cell and an increase in the flux in the opposite direction. The results concerning mucosal efflux of alanine are apparently inconsistent with the carrier model for alanine transport at this border. Alanine transfer across the serosal membrane appeared to involve a facilitated transfer mechanism. Alanine movement at the serosal side of the cell was not influenced by Na+.

Alanine↗
PubMed1976

Effects of cholera toxin on cellular and paracellular sodium fluxes in rabbit ileum.

The diarrhea observed in patients with cholera is known to be related to secretion of water and electrolytes into the intestinal lumen. However, the exact mechanisms involved in these secretory processes have remained unclear. Although it is clear that purified toxin acts on epithelial cell metabolism, its activity on Na+ transport across intestinal mucosa is equivocal: reported either to prevent net Na+ absorption or to cause net secretion of Na+ from serosa to mucosa. Since total transmural Na+ fluxes across "leaky" epithelia involve very significant movement via a paracellular shunt pathway, we studied the effects of cholera toxin on the cellular and paracellular pathways of Na+ movement. Unidirectional Na+ fluxes were examined as functions of applied potential in control tissues and in tissues from the same animal treated with purified cholera toxin. Treatment of rabbit ileum in vitro with toxin simulated the cellular component of serosa-to-mucosa Na+ flux (from 2.41 +/- 0.49 muequiv./h per cm2 under control conditions to 4.71 +/- 0.43 muequiv./h per cm2 after treatment with toxin, P less than 0.01). The effect of cholera toxin on Na+ movement through the cells from mucosa to serosa appeared to be insignificant. Finally, a marked decrease in the Na+ permeability (P less than 0.01) and no detectable significant changes in transference number for Na+ of the paracellular shunt pathway were observed following treatment with cholera toxin. These results provide direct evidence for the hypothesis that purified cholera toxin stimulates active sodium secretion but has minimal effect on sodium absorption.

Animals↗
PubMed1976

Sodium transport by the colon of Bufo marinus: Na uptake across the mucosal border.

Na transport by the isolated toad colon has been studied by measuring transmural Na fluxes and by direct measurement of the Na influx across the mucosal border. Net Na transport accounts for 88% of the short circuit current in the presence and in the absence of exogenous aldosterone. Na influx across the mucosal border appears to consist of two components. One component is highly correlated with short circuit current, is a saturable function of mucosal Na concentration, and is inhibited by lithium ions in the mucosal medium. The second component is a linear function of mucosal Na concentration, is unaffected by lithium, and is apparently not related to net Na transport by the tissue.

Aldosterone↗
PubMed1975

Regulation of protein phosphorylation and sodium transport in toad bladder.

It is well established that active sodium-ion transport and water flow across isolated toad bladder are increased by antidiuretic hormone (ADH) and by cAMP. These agents were also observed in previous studies to cause changes in the amount of radioactive phosphate in a specific protein in the toad bladder. This protein, found by SDS-polyacrylamide gel electrophoresis of toad bladder epithelial preparations, had an apparent molecular weight of 49,000 daltons. In the present study, a correlation was found between the ability of a variety of substances to affect the amount of radioactive phosphate in this 40,000-dalton protein and their ability to alter the rate of sodium transport. Thus several agents (ADH, cAMP, theophylline, adenine, prostaglandin E1, and Mn Cl-2) caused a decrease in the amount of radioactive phosphate in the 49,000-dalton protein and also stimulated active sodium transport across the bladder. Conversely, ZnCl-2 produced an increase in the amount of radioactive phosphate in this protein and an inhibition of sodium transport. With each of these agents, the time-course of change in phosphorylation of this protein was, in general, similar to that for sodium transport. A second phosphoprotein, with an apparent molecular weight of about 42,000 daltons, showed changes in parallel with, but less extensive than, those observed in the 49,000 dalton protein. There was no consistent relationship between changes in level of phosphorylation of either in the 49,000- or 42,000- dalton protein and changes in osmotic water permeability. The results are compatible with the possibility that regulation by ADH and by cAMP of sodium transport in the toad bladder epithelium may be mediated through regulation of the amount of phosphate in a specific protein.

Adenine↗
PubMed1974

Characteristics of sodium flux from serosa to mucosa in rabbit ileum.

Sodium flux from serosa to mucosa, J(sm) (Na) in rabbit ileum in vitro has been studied as a function of applied electrical potential at equal sodium concentrations in the bathing solutions. The results indicate that J(sm) (Na) involves two pathways, a diffusional flux through a paracellular shunt pathway and a flux that is independent of applied potential and presumably involves a transcellular pathway. The latter pathway comprises approximately 25 % of J(sm) (Na) in Ringer's solution containing 10 mM glucose and 25 mM bicarbonate. It is stimulated significantly by theophylline unaffected by removal of glucose or addition of ouabain but is reduced to negligible values by anoxia, dinitrophenol, and replacement of all chloride and bicarbonate by isethionate. Thus this component of J(sm) (Na) has a number of characteristics consistent with involvement in a specific secretory process mediating an electrically neutral secretory transport of sodium plus anion from serosa to mucosa. In addition to stimulating this process, theophylline significantly reduced the permeability of the paracellular shunt pathway to sodium.

Alkanesulfonates↗
PubMed1974

Structure-affinity relationships of substrates for the neutral amino acid transport system in rabbit ileum.

The apparent affinities of various amino acids for the neutral amino acid transport system in rabbit ileum were determined by measuring the inhibition of L-methionine-(14)C influx across the brush border membrane. The apparent affinity was very low for compounds lacking an alpha-amino group, compounds with the alpha-hydrogen substituted by a methyl group, D-compounds, compounds with tertiary branching in the side chain, compounds with either a positive or negative charge in the side chain, and in most cases, compounds with a hydrophilic moiety in the side chain. High apparent affinities were exhibited by compounds with unbranched carbon or carbon-sulfur side chains. Branched compounds such as valine and leucine exhibited affinities which correlate with binding of only the linear portion of the side chain. The calculated change in free energy of binding is 370 cal/mol/CH(2) group which suggests the binding region for the side chain is partially hydrophobic. The affinities of families of analogues, derivatives of cysteine, methionine, serine, alanine, valine, and phenylalanine, correlate with their calculated octanol/water partition coefficients and are also correlated with apparent structural and electronic differences between families. The data permit a preliminary description of the functional geometry of the neutral amino acid transport site. The site contains a region for binding the alpha-amino group, alpha-carboxyl group, and side chain. The regions about the alpha-amino group and alpha-hydrogen are quite sterically limited. The side chain binding region is hydrophobic in nature and appears to be shallow, binding only the linear portion of branched or ring compounds.

Amino Acids↗
PubMed1973

Regulation of phosphorylation of a specific protein in toad-bladder membrane by antidiuretic hormone and cyclic AMP, and its possible relationship to membrane permeability changes.

Phosphorylation of a specific protein was decreased in intact toad bladders by exposure to either antidiuretic hormone or monobutyryl cyclic AMP. The decrease in phosphorylation caused by these agents preceded the change in electrical potential difference (an indicator of the rate of sodium ion transport) observed in response to the same compounds. The addition of cyclic AMP to homogenates of toad bladder led to a decrease in phosphorylation of the same, or a similar, protein. In subcellular fractionation studies, the effect of cyclic AMP on the phosphorylation of this protein was observed in those fractions rich in membrane fragments, but not in the nuclear or cell-sap fractions. These and other results are compatible with the possibility that the regulation by vasopressin and cyclic AMP of sodium and/or water transport in toad bladder may be mediated through regulation of the phosphorylation of this specific protein.

Animals↗
PubMed1973

Response of the frog skin to steady-state voltage clamping. II. The active pathway.

Active Na transport across frog skin was separated from passive Na movement utilizing urea influx as a measure of passive (shunt) permeability. In this manner, the response of the overall active Na transport system to an applied potential was determined over a range from +200 mV to -100 mV. Active Na transport displays saturation as a function of applied potential, and both the level of saturation and the potential at which it is achieved are functions of the Na concentration in the external solution. The saturation with potential appears to involve a different step in the transport process than the saturation of Na flux as a function of external Na concentration. The observations can be qualitatively described by either a one-barrier or two-barrier model of the Na transport system.

Animals↗
PubMed1973

Inhibition of amino acid transport in rabbit intestine by p-chloromercuriphenyl sulfonic acid.

Influx of phenylalanine across the brush border of rabbit intestine is markedly reduced by treatment with 5 mM p-chloromercuriphenyl sulfonate (PCMBS). The effect is rapidly and completely reversed by dithiothreitol. Phenylalanine influx into PCMBS-treated tissue can be competitively inhibited by other neutral amino acids and follows saturation kinetics. PCMBS causes an increase in the apparent Michaelis constant from the value observed in control tissue but does not alter the maximal influx significantly. Treatment of the tissue with PCMBS leads to a significant reduction in the Na-sensitivity of the transport, and a number of results indicate that the major effect of the reagent is to cause a marked reduction in the affinity of the transport system for Na. The transport system can be partially protected against reaction with PCMBS by phenylalanine and tryptophan but not by methionine or norleucine. The results suggest that PCMBS reacts with a sulfhydryl group in the region of the transport site and may alter conformational changes associated with the binding of substrates.

Amino Acids↗
PubMed1972

Response of the frog skin to steady-state voltage clamping. I. The shunt pathway.

Properties of the shunt pathway (a pathway in parallel to the Na transport system) in frog skin have been examined. The permeability of this shunt to urea increases markedly when the skin is depolarized to -100 mv (inside negative) but hyperpolarization to +100 mv produces no change in urea permeability compared to short-circuit conditions. The permeability increase at depolarizing potentials is dependent on the external solute concentration and is considerably reduced by the presence of external Ca. Neither urea permeability nor its response to changes in potential difference are affected by complete inhibition of Na transport by ouabain. In ouabain-poisoned skins, movements of Na, K, Cl, and mannitol through the shunt change in parallel with urea movements. Ion fluxes under these conditions and their response to potential can be described by the constant field equation. The selectivity of the shunt is in the order Cl > urea > K > Na > mannitol and this order does not appear to be affected by the absolute magnitude of the shunt permeability. Arguments are presented suggesting that the pathway is mainly between cells and that its permeability may be affected by cell swelling.

Animals↗