Effects of amiloride on active sodium transport by the isolated frog skin: evidence concerning site of action

Salako, L.A.; Smith, Anthony J.

doi:10.1111/j.1476-5381.1970.tb09878.x

Cited by 58 publications

(17 citation statements)

References 22 publications

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“…Decrease in Na § influx associated with increase in backflux (12 series) was observed by Biber, Chez and Curran [5] in ouabain-treated skins. Decrease in influx associated with decrease in backflux (10 and 11 series) was noted by Salako and Smith [28] in skins treated with amiloride. Increase and decrease in Na § influx with no clear-cut changes in Na § outflux was recently described by Huf [21], suggesting more separate pathways.…”

Section: ( C) Transmembrane Fluxesmentioning

confidence: 83%

Computer simulation of sodium fluxes in frog skin epidermis

Huf

1974

J. Membrain Biol.

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Summary. The operation of a seven-compartment model is described with respect to flows of Na + within and across this system, simulating published results obtained on frog skin. The seven compartments represent: one outside and one inside solution compartment; the subcorneal space; the first reacting cell layer (1.RCL); the remaining cell compartment; the non-, or slowly exchangeable Na + compartment; the extracellular space. Assuming reasonable volumes for the epidermal compartments and further chosing, by trial and error, appropriate rate constants, a set of seven simultaneous linear differential equations was solved by the application of the Continuous System Modeling Program (CSMP), using an IBM 1130 computer. Initial conditions for influx, backflux and net flux were taken which correspond to [Na+]0; [Na+]i= 115 mM. Print-out data were obtained at 0.5-min intervals for 30 min, when steady states were obtained in 13 models studied, varying certain k's thus simulating actions of chemical agents (hormones; drugs). Simulation was achieved with regard to rate of influx, backflux and net flux, steady-state time (30 min), and electrical potentials. In addition, this approach gave detailed information on Na + pool sizes and their variations with changes in k's. These results are compared to published data on frog skin and good agreement between operation of skin epidermis and model was found.During the last decade the three-compartment model proposed by Curran, Herrera and Flanigan [14] has frequently been used in kinetic studies of movement of ions across epithelial membranes. Some applications have recently been reviewed [38]. In this model, compartments 1 and 3 represent, respectively, the outside and the inside fluid compartments, and compartment 2 is an epithelial compartment located between two major barriers to Na § movement. From light-and electron-microscopic studies on frog skin epidermis [18,19,[32][33][34] it would appear that in inward and outward movement of Na + several epithelial compartments should be considered as significant parts of a flow model. For instance, Zerahn [43] has found it useful to consider three epithelial compartments in the interpreta-

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Section: ( C) Transmembrane Fluxesmentioning

confidence: 83%

Computer simulation of sodium fluxes in frog skin epidermis

Huf

1974

J. Membrain Biol.

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“…The mechanism of action of this substance has been worked out mainly from studies using amphibian sodium transporting epithelia (Bentley, 1968;Ehrlich & Crabbe, 1968;Salako & Smith, 1970;Dorge & Nagel, 1970;Biber, 1971;Cuthbert, 1976a). It is clear that amiloride blocks passive sodium entry into the transporting compartment of epithelia and not the processes of active sodium extrusion across the serosal surfaces.…”

Section: Introductionmentioning

confidence: 99%

Effects of Some Pyrazinecarboxamides on Sodium Transport in Frog Skin

Cuthbert

Fanell

1978

British J Pharmacology

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1 The inhibitory effect of amiloride (N-amidino-3,5-diamino-6-chloropyrazinecarboxamide) on sodium transport in isolated skin of frog has been compared with 17 of its analogues. The dissociation constant of amiloride for passive sodium channels was 181.9 + 8.9 nm, and the maximal percentage inhibition of sodium transport was 101.3 + 0.4% (means of 123 measurements) when measured at a sodium concentration of 111 mm. 2 The N-benzylamidino and N-o-chlorobenzylamidino compounds had affinities approximately 20 times larger than those for amiloride, and produced maximal inhibition of transport. 3 Substitution of chlorine in the 6-position by other halogens showed that the bromo-compound was equally active to amiloride, whereas the iodo derivative had an affnity equal to 15%'of that for amiloride. 4 Substitution in the 5-amino group in 10 compounds reduced the affinities to less than 1% of that of amiloride, without affecting their ability to produce complete inhibition of transport. 5 N-Amidino-3,5-diaminopyrazinecarboxamide was unique in that it produced an unusual concentration-response relationship.

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“…Effect ofamiloride on I~. Amiloride, a pyrazine diuretic, inhibits Na + (Baer, Jones, Spitzer & Russo, 1967), toad bladder (Bentley, 1968), toad colon and skin (Crabbd & Erlij, 1968;Erlij & Crabb6, 1968) frog skin (Salako & Smith, 1970), and rabbit colon (S. Schultz, personal communication). However, there is no so-called "leaky epithelium " (Fr6mter & Diamond, 1972) in which an effect has been demonstrated.…”

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confidence: 97%

Na+ transport by rabbit urinary bladder, a tight epithelium

1976

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By in vitro experiments on rabbit bladder, we reassessed the traditional view that mammalian urinary bladder lacks ion transport mechanisms. Since the ratio of actual-to-nominal membrane area in folded epithelia is variable and hard to estimate, we normalized membrane properties to apical membrane capacitance rather than to nominal area (probably 1 muF approximately 1 cm2 actual area). A new mounting technique that virtually eliminates edge damage yielded resistances up to 78,000 omega muF for rabbit bladder, and resistances for amphibian skin and bladder much higher than those usually reported. This technique made it possible to observe a transport-related conductance pathway, and a close correlation between transepithelial conductance (G) and short-circuit current (Isc) in these tight epithelia. G and Isc were increased by mucosal (Na+) [Isc approximately 0 when (Na+) approximately 0], aldosterone, serosal (HCO-3) and high mucosal (H+); were decreased by amiloride, mucosal (Ca++), ouabain, metabolic inhibitors and serosal (H+); and were unaffected by (Cl-) and little affected by antidiuretic hormone (ADH). Physiological variation in the rabbits' dietary Na+ intake caused variations in bladder G and Isc similar to those caused by the expected in vivo changes in aldosterone levels. The relation between G and Isc was the same whether defined by diet changes, natural variation among individual rabbits, or most of the above agents. A method was developed for separately resolving conductances of junctions, basolateral cell membrane, and apical cell membrane from this G--Isc relation. Net Na+ flux equalled Isc. Net Cl- flux was zero on short circuit and equalled only 25% of net Na+ flux in open circuit. Bladder membrane fragments contained a Na+-K+-activated, ouabain-inhibited ATPase. The physiological significance of Na+ absorption against steep gradients in rabbit bladder may be to maintain kidney-generated ion gradients during bladder storage of urine, especially when the animal is Na+-depleted.

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Effects of amiloride on active sodium transport by the isolated frog skin: evidence concerning site of action

Cited by 58 publications

References 22 publications

Computer simulation of sodium fluxes in frog skin epidermis

Computer simulation of sodium fluxes in frog skin epidermis

Effects of Some Pyrazinecarboxamides on Sodium Transport in Frog Skin

Na+ transport by rabbit urinary bladder, a tight epithelium

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