Abstract
We have synthetised a series of oxidised apomorphine derivatives (orto and para quinones 2-5), in order to analyse their vascular activity. We have performed radioligand binding assays on rat cortical membranes and functional studies on rat aortic rings. Instead the relaxant activity exhibited by (R)-apomorphine, o-quinones 2, 4, show contractile activity dependent on endothelium in rat aortic rings. Compound 2, the main metabolite of (R)-apomorphine auto-oxidation, was the product which showed enhanced contractile activity by a complex mechanism related to activation of Ca(2+) channels through release and/or inhibition of endothelial factors. Moreover, this compound disrupts the endothelial function as shows the lack of response to acetylcholine observed in vessels pretreated with it.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / pharmacology
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Animals
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Aorta / drug effects
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Aorta / physiology
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Apomorphine / chemistry*
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Apomorphine / metabolism
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Apomorphine / pharmacology*
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Calcium Channels, L-Type / metabolism
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Cerebral Cortex / metabolism
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Dose-Response Relationship, Drug
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / metabolism
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Enzyme Inhibitors / pharmacology
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Female
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Nitric Oxide Synthase / antagonists & inhibitors
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Oxidation-Reduction
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Quinones / chemistry
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Quinones / metabolism
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Quinones / pharmacology
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Radioligand Assay
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Rats
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Rats, Wistar
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Receptors, Adrenergic, alpha / metabolism
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Receptors, GABA-A / metabolism
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Stereoisomerism
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Vasoconstriction / drug effects*
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Vasoconstriction / physiology
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Vasoconstrictor Agents / pharmacology*
Substances
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Calcium Channels, L-Type
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Enzyme Inhibitors
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Quinones
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Receptors, Adrenergic, alpha
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Receptors, GABA-A
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Vasoconstrictor Agents
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Nitric Oxide Synthase
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Apomorphine
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Acetylcholine