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J M Edwardson

Publications and source records attributed to J M Edwardson.

4 recordsLinked to original sources
PubMed1979

Synthesis, properties and biological activity of tritiated N-benzylamidino-3,5-diamino-6-chloro-pyrazine carboxamide -- a new ligand for epithelial sodium channels.

A method is described for the synthesis and purification of tritiated N-benzylamidino-3,5-diamino-6-chloro-pyrazine carboxamide (benzamil). The tritium was inserted at the meta position of the benzyl ring, from which it apparently does not exchange with solvent hydrogen. When stored in ethanol at -4 degrees C the radioligand remains stable for at least 15 months. The pharmacology of benzamil is very similar to that of amiloride in terms of its effects on sodium transporting epithelia except that it has a higher affinity. The affinity of benzamil for sodium channels in amphibian epithelia in the absence of sodium is approximately 10(9) M-1. The new ligand can be used to label sodium channels in epithelia, and may be useful in channel isolation procedures.

Amiloride↗
PubMed1979

Estimation of the density of sodium entry sites in frog skin epithelium from the uptake of [3H]benzamil.

1. The inhibition of short circuit current in frog skin by benzamil (N-benzyl-amidino-3,5-diamino-6-chloropyrazine carboxamide) was investigated. When skins were bathed on both sides by Ringer solution (pH 7.6) the affinity was 5 x 10(7) M-1. When the sodium concentration was reduced to 1.1 mM and the pH adjusted to 6.5 the affinity increased to 8.5 x 10(8) M-1. 2. A method is described for measuring uptake of [3H]benzamil into the mucosal (outer) surface of pieces of isolated epithelium, 0.95 cm2 in area, under open circuit conditions. 3. The relation of [3H]benzamil uptake at the mucosal surface to its concentration was measured in solutions containing 1.1 mM-sodium and adjusted to pH 6.5. Uptake could be resolved into a linear component (10.2 f-mole nM-1) and a saturable component (21.5 f-mole cm-2) with a half saturating concentration of 1 nM. 4. In the presence of amiloride (1 microM) or unlabelled benzamil (1 microM) uptake was linear with concentration, and was, respectively, 9.2 f-mole nM-1 and 8.8 f-mole nM-1. When the pH was reduced to 3.5 uptake was again linear but reduced to 3.3 f-mole nM-1. 5. The identity of the saturable component of [3H]benzamil uptake to sodium entry sites is discussed. The results suggest a sodium entry site density of around 130 micron-2 of mucosal surface.

Amiloride↗