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- Title
Chlorpromazine Binding to Na<sup>+</sup>, K<sup>+</sup>-ATPase and Photolabeling: Involvement of the Ouabain Site Monitored by Fluorescence.
- Authors
Guevara, Elmer A. C.; de Lourdes Barriviera, Maria; Hassón-Voloch, Aída; Louro, Sonia R. W.
- Abstract
This work reports the results of ultraviolet irradiation on the interaction of the phototoxic antipsychotic drug chlorpromazine (CPZ) with the sodium pump Na+, K+-ATPase. The study was performed by monitoring the fluorescence modifications of CPZ itself and of the specific probe anthroylouabain (AO). CPZ association with Na+, K+-ATPase was found to modify the kinetics of CPZ-photodegradation. It was demonstrated that UV irradiation produces a stable fluorescent photoproduct of CPZ covalently bound to Na+, K+-ATPase. The fluorescent probe AO, which specifically binds to the extracellular ouabain site of the pump, was used to localize the CPZ binding site. UV-irradiation of AO-labeled Na+, K+-ATPase treated with CPZ at concentration about 20 μ M produced dose-dependent modifications of the AO fluorescence, e.g. increased quantum yield and blue shift. The results demonstrated that CPZ binds near the ouabain site. The photo-induced reaction of CPZ with AO-labeled Na+, K+-ATPase protected the ouabain site from the aqueous environment. It was also found that UV irradiation of CPZ-treated enzyme obstructs the binding of AO, which suggested occlusion of the ouabain site. This effect can be evaluated for a potential use of CPZ in photochemotherapy.
- Subjects
ULTRAVIOLET radiation; IRRADIATION; CHLORPROMAZINE; SODIUM; FLUORESCENCE
- Publication
Photochemistry & Photobiology, 2007, Vol 83, Issue 4, p914
- ISSN
0031-8655
- Publication type
Article
- DOI
10.1111/j.1751-1097.2007.00077.x