1996
DOI: 10.1007/s004240050196
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Blockade of epithelial Na+ channels by triamterenes — Underlying mechanisms and molecular basis

Abstract: The three subunits (alpha, beta, gamma) encoding for the rat epithelial Na+ channel (rENaC) were expressed in Xenopus oocytes, and the induced Na+ conductance was tested for its sensitivity to various triamterene derivatives. Triamterene blocked rENaC in a voltage-dependent manner, and was 100-fold less potent than amiloride at pH 7.5. At -90 mV and -40 mV, the IC50 values were 5 microM and 10 microM, respectively. The blockage by triamterene, which is a weak base with a pKa of 6.2, was dependent on the extrac… Show more

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Cited by 36 publications
(15 citation statements)
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References 16 publications
(26 reference statements)
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“…The amiloride-sensitive portion of the cur- rent (10 M amiloride added to the bath) was much larger in the oocytes expressing wt ␣,␤,␥rENaC (63 Ϯ 8%) than in oocytes expressing ␣⌬278 -283,␤,␥rENaC (19 Ϯ 3%). These observations are consistent with those reported by Busch et al (23). A portion of the base-line current in water-injected oocytes was also found to be amiloride-sensitive (17 Ϯ 4%).…”
Section: Resultssupporting
confidence: 83%
“…The amiloride-sensitive portion of the cur- rent (10 M amiloride added to the bath) was much larger in the oocytes expressing wt ␣,␤,␥rENaC (63 Ϯ 8%) than in oocytes expressing ␣⌬278 -283,␤,␥rENaC (19 Ϯ 3%). These observations are consistent with those reported by Busch et al (23). A portion of the base-line current in water-injected oocytes was also found to be amiloride-sensitive (17 Ϯ 4%).…”
Section: Resultssupporting
confidence: 83%
“…4-Hydroxytriamterene sulfate represents an active sulfate conjugate metabolite of triamterene. The metabolite has nominally lower intrinsic potency and a lower free fraction; however, its plasma concentrations are well in excess of parent and thus it contributes to effect (Busch et al, 1996).…”
Section: A Metabolic Reactions That Can Yield Active Metabolitesmentioning
confidence: 99%
“…The metabolic reactions are catalyzed by CYP1A2 and platelet phenol sulfotransferase. Accounting for differences in free fraction and estimates of intrinsic potency (Busch et al, 1996), it can be estimated that the metabolite contributes approximately half of the activity of the parent drug. The metabolite has been shown to be active in animal models (Voelger, 1991).…”
mentioning
confidence: 99%
“…Twoelectrode voltage-clamp recordings were performed at a holding potential of Ϫ80 mV. The data were filtered at 10 Hz and recorded with MacLab digital-to-analog converter and software for data acquisition and analysis (AD Instruments, Castle Hill, Australia) (31). In all experiments oocytes were superfused with ND96 solution (96 mM NaCl͞2 mM KCl͞1.8 mM CaCl 2 ͞1 mM MgCl 2 ͞5 mM Hepes, pH 7.4).…”
Section: Coexpression Of Hsgk With Rat Epithelial Na ؉ Channel (Enac)mentioning
confidence: 99%