Abstract
The ability of putative selective irreversible ligands SZL-49 (1-(4-amino-6,7-dimethoxy-2,5-diene-2-carbonyl)) and CEC (chlorethylclonidine), for alpha 1A and alpha 1B adrenoceptor subtypes, respectively, to affect alpha 1-adrenoceptors of canine aorta microsomal membranes was investigated. These membranes contain an apparently homogeneous population of [3H]prazosin binding sites. SZL-49, like phenoxybenzamine, abolished all binding of [3H]prazosin. CEC abolished 75% of the prazosin binding sites under the most stringent conditions we applied. However, the remaining 25% of binding sites was identical in affinity for prazosin with control membranes, and competition studies of other subtype-selective ligands revealed unchanged ability to complete against CEC-sensitive and -insensitive sites. We concluded that SZL-49 and CEC are not alpha 1A- and alpha 1B-adrenoceptor selective under in vitro conditions. Our data led to the hypothesis that canine aortic membranes contain exclusively alpha 1B-adrenoceptors but that current tools for identifying alpha 1-adrenoceptor subtypes proved inadequate in vitro in this study.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-1 Receptor Antagonists
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Adrenergic alpha-Agonists / pharmacokinetics
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Adrenergic alpha-Agonists / pharmacology
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Adrenergic alpha-Antagonists / pharmacokinetics
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Adrenergic alpha-Antagonists / pharmacology
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Alkylating Agents / pharmacology*
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Animals
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Aorta / drug effects
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Aorta / metabolism
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Binding, Competitive / drug effects
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Clonidine / analogs & derivatives
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Clonidine / pharmacology
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Dioxanes / pharmacology
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Dogs
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Female
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In Vitro Techniques
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Male
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Mesenteric Veins / drug effects
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Mesenteric Veins / metabolism
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Oxymetazoline / pharmacology
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Prazosin / analogs & derivatives
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Prazosin / pharmacokinetics
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Prazosin / pharmacology
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Radioligand Assay
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Receptors, Adrenergic, alpha-1 / drug effects
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Receptors, Adrenergic, alpha-1 / metabolism*
Substances
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Adrenergic alpha-1 Receptor Antagonists
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Adrenergic alpha-Agonists
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Adrenergic alpha-Antagonists
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Alkylating Agents
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Dioxanes
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Receptors, Adrenergic, alpha-1
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SZL 49
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chlorethylclonidine
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Oxymetazoline
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(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
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Clonidine
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Prazosin