Correlation between vasoconstrictor roles and mRNA expression of alpha1-adrenoceptor subtypes in blood vessels of genetically engineered mice.

Détails

ID Serval
serval:BIB_5427A798B715
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Correlation between vasoconstrictor roles and mRNA expression of alpha1-adrenoceptor subtypes in blood vessels of genetically engineered mice.
Périodique
British Journal of Pharmacology
Auteur(s)
Hosoda C., Tanoue A., Shibano M., Tanaka Y., Hiroyama M., Koshimizu T.A., Cotecchia S., Kitamura T., Tsujimoto G., Koike K.
ISSN
0007-1188 (Print)
ISSN-L
0007-1188
Statut éditorial
Publié
Date de publication
2005
Volume
146
Numéro
3
Pages
456-466
Langue
anglais
Résumé
We examined the contribution of each alpha(1)-adrenoceptor (AR) subtype in noradrenaline (NAd)-evoked contraction in the thoracic aortas and mesenteric arteries of mice. Compared with the concentration-response curves (CRCs) for NAd in the thoracic aortas of wild-type (WT) mice, the CRCs of mutant mice showed a significantly lower sensitivity. The pD(2) value in rank order is as follows: WT mice (8.21) > alpha(1B)-adrenoceptor knockout (alpha(1B)-KO) (7.77) > alpha(1D)-AR knockout (alpha(1D)-KO) (6.44) > alpha(1B)- and alpha(1D)-AR double knockout (alpha(1BD)-KO) (5.15). In the mesenteric artery, CRCs for NAd did not differ significantly between either WT (6.52) and alpha(1B)-KO mice (7.12) or alpha(1D)-KO (6.19) and alpha(1BD)-KO (6.29) mice. However, the CRC maximum responses to NAd in alpha(1D)- and alpha(1BD)-KO mice were significantly lower than those in WT and alpha(1B)-KO mice. Except in the thoracic aortas of alpha(1BD)-KO mice, the competitive antagonist prazosin inhibited the contraction response to NAd with high affinity. However, prazosin produced shallow Schild slopes in the vessels of mice lacking the alpha(1D)-AR gene. In the thoracic aorta, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.25 and 8.46, respectively, and in alpha(1B)-KO mice they were 8.49 and 9.13, respectively. In the mesenteric artery, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.34 and 7.47, respectively, and in alpha(1B)-KO mice they were 8.11 and 7.82, respectively. These pharmacological findings were in fairly good agreement with findings from comparison of CRCs, with the exception of the mesenteric arteries of WT and alpha(1B)-KO mice, which showed low affinities to BMY7378. We performed a quantitative analysis of the mRNA expression of each alpha(1)-AR subtype in these vessels in order to examine the correlation between mRNA expression level and the predominance of each alpha(1)-AR subtype in mediating vascular contraction. The rank order of each alpha(1)-AR subtype in terms of its vasoconstrictor role was in fairly good agreement with the level of expression of mRNA of each subtype, that is, alpha(1D)-AR > alpha(1B)-AR > alpha(1A)-AR in the thoracic aorta and alpha(1D)-AR > alpha(1A)-AR > alpha(1B)-AR in the mesenteric artery. No dramatic compensatory change of alpha(1)-AR subtype in mutant mice was observed in pharmacological or quantitative mRNA expression analysis.
Mots-clé
Adrenergic alpha-Antagonists/pharmacology, Animals, Aorta, Thoracic/drug effects, Aorta, Thoracic/metabolism, Gene Expression Regulation/drug effects, Indoles/pharmacology, Male, Mesenteric Arteries/drug effects, Mesenteric Arteries/metabolism, Mice, Mice, Knockout, Norepinephrine/pharmacology, Piperazines/pharmacology, Prazosin/pharmacology, RNA, Messenger/analysis, RNA, Messenger/metabolism, Receptors, Adrenergic, alpha-1/genetics, Receptors, Adrenergic, alpha-1/metabolism, Vasoconstriction/drug effects
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 14:09
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