Central hypotensive effects of the alpha2a-adrenergic receptor subtype.
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.
MacMillan
L B
LB
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
Hein
L
L
Smith
M S
MS
Piascik
M T
MT
Limbird
L E
LE
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001933:Brain Stem / Q000502:physiology; D000068438:Brimonidine Tartrate; D018390:Gene Targeting; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D020926:Medetomidine; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017354:Point Mutation; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C547769:Adra2a protein, mouse; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D007093:Imidazoles; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; D020926:Medetomidine