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- W187897308 abstract "This study investigates the interactions of sibutramine, a hypophagic drug non-selective inhibitor of norepinephrine (NE) and 5-HT uptake, with the α1-ARs subtypes of the rat vas deferens (α1A), spleen (α1B) and aorta (α1D) and with human α1-ARs subtypes expressed in HEK 293 cells. Sibutramine potentiated the contractions induced by NE in the vas deferens, consistent with an indirect sympathomimetic action. In the rat spleen, sibutramine (up to 100 μM) was unable to affect the contractions induced by NE, suggesting it is inactive at α1B-ARs. In rat aorta sibutramine 3 to 100 μM competitively antagonized the contractions induced by NE (Schild slope = 0.95 ± 0.05; pA2 = 5.5 ± 0.1) indicating it interacts with α1D-ARs. Sibutramine inhibited the specific binding of [3H]-prazosin to membranes from HEK cells expressing α1A-ARs and α1B-ARs with very low affinities (pKi ≈ 3.5). Low concentrations of sibutramine (30 nM to 1 μM) partially inhibited (≈50%) the specific binding of [3H]-prazosin to membranes from HEK cells expressing α1D-ARs. In dissociation experiments, a low concentration of sibutramine (0.3 μM) increased by 5-fold the dissociation of [3H]-prazosin from membranes of HEK cells expressing α1D-ARs whereas sibutramine 10 μM delayed it by 3-fold. Although presenting complex behavior in radioligand binding assays, sibutramine interacts selectively with native and recombinant α1D-ARs." @default.
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- W187897308 date "2008-03-01" @default.
- W187897308 modified "2023-10-18" @default.
- W187897308 title "Complex interactions of sibutramine with α 1D ‐adrenoceptors" @default.
- W187897308 doi "https://doi.org/10.1096/fasebj.22.1_supplement.726.1" @default.
- W187897308 hasPublicationYear "2008" @default.
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