Wirkungscharakteristika eines neuen Aeylguanidins — Amiloride-HCL (MK 870) — an der isolierten Haut von Amphibien

Eigler, J; Kelter, J.; Renner, E.

doi:10.1007/bf01746103

Cited by 63 publications

(21 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fig. 1 of the skin (Eigler, Kelter & Renner, 1967;D6rge & Nagel, 1970;Biber, 1971; and others), inhibited the Na uptake in skins from distilled-wateradapted animals. However, Na uptake in skins from 115 and 200 mmNaCl-adapted animals was not affected by the amiloride.…”

Section: Resultsmentioning

confidence: 87%

Salt‐induced changes in sodium transport across the skin of the euryhaline toad, Bufo viridis.

Katz¹

1975

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. Euryhaline toads (Bufo viridis) were adapted to either distilled water, 115 or 200 mm-NaCl solutions. Na transport across the skin of these animals was studied in in vitro preparations.2. Salinity adaptation caused a reduction in transepithelial potential and short-circuit current across the skin, and increased its electrical resistance.3. Na influx across the skin was decreased. The reduction accounted fairly well for the measured reduction in short-circuit current.4. Short-term Na uptake at the outer barrier of the skin was greatly reduced in preparations from salt adapted animals. Amiloride, which usually inhibits Na uptake, did not affect it in skins from salt adapted toads.5. Sodium conductance decreased by a factor of three in skins from 115 mM-NaCl adapted toads, and to zero in skins from 200 mM-NaCl adapted animals. Shunt conductance was only little affected by the salinity of adaptation.6. 'Amiloride-sensitive component' of transepithelial Na transport was 55, 21.5, and 4*5,uA/cm2 in skins from toads which were adapted to distilled water, 115, and 200 mm-NaCl solutions, respectively. 7. It is concluded that the effect of salinity adaptation on the skin of the toad is to reduce the number of Na selective sites at the outer barrier. This change is reflected in a decrease in the 'amiloride-sensitive component' of Na transport across the skin, and could not be increased by aldosterone. Other changes may occur as secondary to that.

show abstract

Section: Resultsmentioning

confidence: 87%

Salt‐induced changes in sodium transport across the skin of the euryhaline toad, Bufo viridis.

Katz¹

1975

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…In other studies, amiloride reduced short-circuit current and influx of sodium ions into isolated membranes capable of active sodium transport (Eigler, Kelter, Renner, 1967;Bentley, 1968;Salako & Smith, 1970 a, b). The effective in vitro concentration was 0-1 /,M to 10 gM and human urinary levels of 10 uM have also been reported (Baer & Foltz, 1969).…”

Section: Discussionmentioning

confidence: 85%

Kinetics and bioavailability of two formulations of amiloride in man

Smith

1973

British J Pharmacology

View full text Add to dashboard Cite

Summary1. Two formulations of [1'C]-amiloride were compared in six oedema-free subjects in single-dose (20 mg) studies separated by a two-week interval.2. Calculation of the elimination rate constant (Ke), half-life (T*) and apparent volume of distribution (Vd) from serum and urinary data showed no significant difference between the two formulations. The Vd values (350 to 380 litres) were greater than total body fluid volume suggesting extravascular sequestration of amiloride. 3. Serum and urinary amiloride levels were similar with both formulations. Pharmacokinetic parameters were similar to those of an earlier report based on one formulation. 4. The calculated amiloride concentration in the renal distal tubule (3 ,uM to 20 /.M) was similar to, but higher than, reported in vitro concentrations of amiloride which reduced sodium transport in isolated membranes. IitroductionAmiloride is an effective natriuretic and diuretic compound which also reduces urinary potassium loss (Baer, Jones, Spitzer & Russo, 1967; Baba, Lant, Smith, Townshend & Wilson, 1968). In the course of a study of the bioavailability of two different formulations of amiloride, an opportunity was provided to confirm earlier work on its clinical pharmacology (Weiss, Hersey, Dujovne & Bianchine, 1969) and to compare effective urinary concentrations of the diuretic in man with those required to inhibit sodium transport in animal tissues in vitro. MethodsThe two formulations of amiloride were administered in random sequence to six oedema-free subjects in single-dose studies separated by a two-week interval. SubjectsThere were six male subjects, aged 35 to 56 years (mean 49 years) without cardiovascular, renal or hepatic disease. Four convalescent patients, who had had orthopaedic operations at least four weeks previously, agreed to participate in the study. The other two subjects were healthy members of departmental staff.

show abstract

“…Amiloride is a substituted pyrazine carboxamide developed as a result of a search for a nonsteroidal natriuretic, antikaluretic agent (31). It has become useful as a probe of membrane ion transport since its effects upon short-circuit current, a reflection of active sodium transport, were first demonstrated in amphibian tissues (32,33). It has been shown subsequently that amiloride acts upon susceptible amphibian (bladder, colon, skin) and mammalian (distal nephron, colon, salivary duct) sites to rapidly and reversibly inhibit permeability to sodium at the mucosal surface or apical cell borders (34).…”

Section: Resultsmentioning

confidence: 99%

Amiloride inhibits mammalian renal kallikrein and a kallikrein-like enzyme from toad bladder and skin.

Margolius¹,

Chao²

1980

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Renal kallikrein is localized in luminal plasma membranes of the mammalian distal nephron and gains access to urine from this site. Its activity is regulated, in part, by aldosterone. These facts led us to study the effects of amiloride, a drug known to inhibit sodium reabsorption and potassium secretion at this site, on kallikrein activity. Amiloride inhibited the esterolytic activity of purified rat or human urinary kallikrein or of rat renal cortical cells upon a synthetic substrate (ID50 = 0.12-0.23 mM). Kinetic analyses showed that the enzyme inhibition was noncompetitive and reversible in nature. The kinin-generating activity of kallikrein acting upon kininogen substrates was also inhibited by amiloride, as measured by bioassay in the rat uterus or guinea pig ileum or by radioimmunoassay of liberated kinins (ID50 = 85 A.tM). No other diuretic drug tested inhibited kallikrein activity, except triamterene, which did so, weakly. In addition, kallikrein-like enzyme activity was discovered in the urinary bladder or skin of Bufo marinus toads and this activity was also inhibited by amiloride. The localization ofthe enzyme and its inhibition by this drug suggest that further study of relationships amongst the glandular kallikrein-kinin system and renal ion and water transport is warranted.

show abstract

Wirkungscharakteristika eines neuen Aeylguanidins — Amiloride-HCL (MK 870) — an der isolierten Haut von Amphibien

Cited by 63 publications

References 4 publications

Salt‐induced changes in sodium transport across the skin of the euryhaline toad, Bufo viridis.

Salt‐induced changes in sodium transport across the skin of the euryhaline toad, Bufo viridis.

Kinetics and bioavailability of two formulations of amiloride in man

Amiloride inhibits mammalian renal kallikrein and a kallikrein-like enzyme from toad bladder and skin.

Contact Info

Product

Resources

About