ISSN:
1432-1424
Keywords:
amiloride
;
toad bladder
;
phenamil
;
sodium channels
;
binding
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
Notes:
Summary Several new amiloride analogues and two reported photoaffinity analogues were tested for irreversible inhibition of short-circuit current,I sc, in toad bladder. Bromoamiloride, a photoaffinity analogue, induced 40% irreversible inhibition at 500 μm after irradiation with ultraviolet light ≥320 nm. Iodoamiloride caused no irreversible inhibition. Of the new analogues tested, only 3,5-diamino-6-chloro-N-[(phenylamino) aminomethylene] pyrazinecarboxamide,phenamil, irreversibly inhibitedI sc at concentrations of 0.05 to 5 μm when added to the mucosal solution. Irreversible inhibition ofI sc by phenamil may be attributed to specific blockage of the mucosal sodium channels, which depended on: 1) time of exposure; 2) mucosal pH: 3) mucosal sodium concentration. For example, 5 μm phenamil irreversibly inhibitedI sc by 38% in 103mm Na at pH 8.6 and nearly 75% in 30mm Na at pH 6.4 after a 40-min exposure. Irreversible inhibition occurred in two phases with time constants of ≤10 min and approximately 140 min. Due to its irreversible nature, phenamil may be used to measure channel density.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01870698
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