Abstract
alpha2-Adrenergic receptors (alpha2ARs) present in the brainstem decrease blood pressure and are targets for clinically effective antihypertensive drugs. The existence of three alpha2AR subtypes, the lack of subtype-specific ligands, and the cross-reactivity of alpha2AR agonists with imidazoline receptors has precluded an understanding of the role of individual alpha2AR subtypes in the hypotensive response. Gene targeting was used to introduce a point mutation into the alpha2aAR subtype in the mouse genome. The hypotensive response to alpha2AR agonists was lost in the mutant mice, demonstrating that the alpha2aAR subtype plays a principal role in this response.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenergic alpha-2 Receptor Agonists
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Adrenergic alpha-Agonists / pharmacology
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Animals
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Antihypertensive Agents / pharmacology
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Base Sequence
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Blood Pressure / drug effects
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Blood Pressure / physiology*
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Brain Stem / physiology
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Brimonidine Tartrate
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Gene Targeting
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Heart Rate / drug effects
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Heart Rate / physiology
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Imidazoles / pharmacology
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Medetomidine
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Point Mutation
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Quinoxalines / pharmacology
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Receptors, Adrenergic, alpha-2 / genetics
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Receptors, Adrenergic, alpha-2 / metabolism
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Receptors, Adrenergic, alpha-2 / physiology*
Substances
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Adra2a protein, mouse
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Adrenergic alpha-2 Receptor Agonists
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Adrenergic alpha-Agonists
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Antihypertensive Agents
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Imidazoles
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Quinoxalines
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Receptors, Adrenergic, alpha-2
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Brimonidine Tartrate
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Medetomidine