Effects of Triamterene and Its Phase I and Phase II Metabolites on Sodium Transport of the Isolated Frog Skin

Abstract

We studied the effects of triamterene (TA) and its phase I and phase II metabolites, p-hydroxytriamterene (OH-TA) and p-hydroxytriamterene sulfuric acid ester (OH-TA ester), on sodium transport in the isolated frog skin. While TA applied to the inside (corial side) surface had no effects on potential difference (PD) and short-circuit current (SCC), TA, OH-TA, and OH-TA ester at a concentration of 10^–5 mol/l significantly decreased SCC by 19, 24 and 16%, respectively, when added to the solution bathing the outside (epithelial side) surface of the skin. In vasopressin-treated skins TA was more effective than OH-TA or OH-TA ester. In aldosterone-treated skins all compounds significantly suppressed SCC, the strongest effect was again exerted by TA. Only minor and transient changes in PD were noted. Inhibition of sodium transport was rapidly reversible when skins were washed with fresh Ringer solution. Thus, OH-TA and OH-TA ester possess qualitatively similar pharmacological activity as TA. The quantitatively smaller effects of OH-TA and OH-TA ester in the hormone-stimulated skin as compared to TA agrees well with their relative natriuretic potency observed in vivo.

Diuretics

“…Amiloride is not subjected to endogenous metabolism (WEISS et al 1969), whereas triamterene, after its intestinal absorption, is rapidly and extensively metabolised to p-hydroxytriamterene and p-hydroxytriamterene sulfate ester (LEHMANN 1965), which are at least as potent as the parent compound (GREBIAN et al 1978;KRAMER et al 1981). Triamterene is excreted as p-hydroxytriamterene sulfate (LEHMANN 1965).…”

Triamterene and the Kidney

“…TA inhibits passive sodium transport from the luminal side of transporting epithelia [25][26][27], resulting in im paired movement of potassium from cell to lumen, since the latter is functionally coupled to sodium movement. Although initial studies suggested that these events in volved inhibition of aldosterone [I], subsequent investi gations have clearly demonstrated that TA can produce these effects either when aldosterone is physiologically suppressed [28] or when it is completely absent as occurs following adrenalectomy [29].…”