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Título

Correlation between mRNA levels and functional role of 1-adrenoceptor subtypes in arteries: evidence of 1L as a functional isoform of the 1A-adrenoceptor

AutorMartí, Daniel; Miquel, Raquel; Ziani, Khalid; Gisbert, Regina; Ivorra, M. Dolores; Anselmi, Elsa; Moreno, Lucrecia; Villagrasa, Victoria; Barettino, Domingo ; D'Ocón, Pilar
Palabras clavealpha1A- alpha1B alpha1D adrenoceptors
chloroethylclonidine
Fecha de publicación10-jun-2005
EditorAmerican Physiological Society
CitaciónAmerican Journal of Physiology Heart and Circulatory Physiology. 2005 Nov;289(5):H1923-H1932
ResumenThe mRNA levels for the three alpha1-adrenoceptor subtypes, alpha1A, alpha1B, and alpha1D, were quantified by real-time RT-PCR in arteries from Wistar rats. The alpha1D-adrenoceptor was prominent in both aorta (79.0%) and mesenteric artery (68.7%), alpha1A predominated in tail (61.7%) and small mesenteric artery (73.3%), and both alpha1A- and alpha1D-subtypes were expressed at similar levels in iliac artery. The mRNA levels of the alpha1B-subtype were a minority in all vessels (1.7-11.1%). Concentration-response curves of contraction in response to phenylephrine or relaxation in response to alpha1-adrenoceptor antagonists on maximal sustained contraction induced by phenylephrine were constructed from control vessels and vessels pretreated with 100 micromol/l chloroethylclonidine (CEC) for 30 min. The significant decrease in the phenylephrine potency observed after CEC treatment together with the inhibitory potency displayed by 8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-8-azaspiro (4,5) decane-7-dionedihydrochloride} (BMY-7378, an alpha1D-adrenoceptor antagonist) confirm the relevant role of alpha1D-adrenoceptors in aorta and iliac and proximal mesenteric arteries. The potency of 5-methylurapidil (an alpha1A-adrenoceptor antagonist) and the changes in the potency of both BMY-7378 and 5-methylurapidil after CEC treatment provided evidence of a mixed population of alpha1A- and alpha1D-adrenoceptors in iliac and distal mesenteric arteries. The low potency of prazosin (pIC50 < 9) as well as the high 5-methylurapidil potency in tail and small mesenteric arteries suggest the main role of alpha1A/alpha1L-adrenoceptors with minor participation of the alpha1D-subtype. The mRNA levels and CEC treatment corroborated this pattern and confirmed that the alpha1L-adrenoceptor could be a functional isoform of the alpha1A-subtype.
Descripción10 pages, 3 figures, 10 tables.-- PMID: 15951348 [PubMed]
Versión del editorhttp://dx.doi.org/10.1152/ajpheart.00288.2005
URIhttp://hdl.handle.net/10261/18345
DOI10.1152/ajpheart.00288.2005
ISSN0363-6135 (print)
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