Chloroethylclonidine reveals that alpha (1 A)-adrenoceptors mediate contraction in aorta of alpha (1 D)-adrenoceptor knockout mice.
1 We have characterized the alpha(1)-adrenoceptor subtypes present in isolated aorta of the alpha(1D)-adrenoceptor knockout (KO) mice, by chloroethylclonidine (CEC)-induced alkylation and their protection by selective alpha(1)-adrenoceptor antagonists. 2 The alpha(1D)-adrenoceptor is involved in the contractile response to noradrenaline in wild type (WT) mouse aorta. 3 In WT mice 5-methylurapidil (5-MU, an alpha(1A)-adrenoceptor antagonist) or BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro[4.5] decane-7,9 dione, a selective alpha(1D)-adrenoceptor antagonist), protected the receptors from CEC-induced (alpha(1B/D)-adrenoceptor) alkylation, the combination of both antagonists resulted in complete protection, while AH11110A (1-[biphenyl-2-yloxy]-4-imino-4-piperidin-1-yl-butan-2-ol, an alpha(1B)-adrenoceptor antagonist) did not protect. 4 In aorta of KO mice there was a 19-fold rightward shift in noradrenaline effective concentration (EC(50)) compared with WT; while 5-MU alone or in combination with AH11110A protected alpha(1)-adrenoceptors to the same extent. 5 The data indicate that alpha(1A)-adrenoceptors mediate contraction and suggest their role in maintaining homeostasis in the alpha(1D)-adrenoceptors KO mice.
Lázaro-Suárez
M L
ML
Facultad de Ciencias Médicas y Biológicas 'Dr. Ignacio Chávez', Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mich., México.
Gómez-Zamudio
J H
JH
Gallardo-Ortíz
I A
IA
Tanoue
A
A
Tsujimoto
G
G
Farias-Rodríguez
V M
VM
Villalobos-Molina
R
R
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009638:Norepinephrine; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents
C434277:AH 11110A; C547714:Adra1a protein, mouse; C547720:Adra1d protein, mouse; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007097:Imines; D010879:Piperazines; D010880:Piperidines; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; C057446:5-methylurapidil; C051731:chlorethylclonidine; C053428:BMY 7378; D003000:Clonidine; D009638:Norepinephrine