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Functional characterization of α 1 ‐adrenoceptor subtypes in vascular tissues using different experimental approaches:a comparative study
Author(s) -
Gisbert Regina,
Madrero Yolanda,
Sabino Valentina,
Noguera M Antonia,
Ivorra M Dolores,
D'Ocon Pilar
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705033
Subject(s) - prazosin , contraction (grammar) , aorta , contractility , antagonist , medicine , endocrinology , chemistry , muscle contraction , alpha (finance) , adrenergic antagonist , artery , biophysics , biology , receptor , surgery , construct validity , patient satisfaction
The α 1 ‐adrenergic responses of rat aorta and tail artery have been analysed measuring the contractility and the inositol phosphate (IP) formation induced by noradrenaline. Three antagonists, prazosin, 5‐methylurapidil (α 1A selective) and BMY 7378 (α 1D selective) have been used in different experimental procedures. Noradrenaline possesses a greater potency inducing contraction and IP accumulation in aorta (pEC 50 ‐contraction=7.32±0.04; pEC 50 ‐IPs=6.03±0.08) than in the tail artery (pEC 50 ‐contraction=5.71±0.07; pEC 50 ‐IPs=5.51±0.10). Although the maximum contraction was similar in both tissues (E max ‐tail=619.1±55.6 mg; E max ‐aorta‐698.2±40.8 mg), there were marked differences in the ability of these tissues to generate intracellular second messengers the tail artery being more efficient (E max ‐tail=1060±147%; E max ‐aorta=108.1±16.9%). Concentration response curves of noradrenaline in presence of antagonist together with concentration inhibition curves for antagonists added before (CICb) or after (CICa) noradrenaline‐induced maximal response in Ca 2+ ‐containing or Ca 2+ ‐free medium have been performed. A comparative analysis of the different procedures as well as the mathematical approaches used in each case to calculate the antagonist potencies, were completed. The CICa was the simplest method to characterize the predominant α 1 ‐adrenoceptor subtype involved in the functional response of a tissue. In aorta, where constitutively active α 1D ‐adrenoeptors are present, the use of different experimental procedures evidenced a complex equilibrium between α 1D ‐ and α 1A ‐adrenoceptor subtypes. The appropriate management of LiCl in IP accumulation studies allowed us to reproduce the different experimental procedures performed in contractile experiments giving more technical possibilities to this methodology.British Journal of Pharmacology (2003) 138 , 359–368. doi: 10.1038/sj.bjp.0705033