6533b82efe1ef96bd1293078

RESEARCH PRODUCT

Functional characterization of α1 -adrenoceptor subtypes in vascular tissues using different experimental approaches:a comparative study

subject

description

The α1-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 (α1A selective) and BMY 7378 (α1D selective) have been used in different experimental procedures. Noradrenaline possesses a greater potency inducing contraction and IP accumulation in aorta (pEC50-contraction=7.32±0.04; pEC50-IPs=6.03±0.08) than in the tail artery (pEC50-contraction=5.71±0.07; pEC50-IPs=5.51±0.10). Although the maximum contraction was similar in both tissues (Emax-tail=619.1±55.6 mg; Emax-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 (Emax-tail=1060±147%; Emax-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 Ca2+-containing or Ca2+-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 α1-adrenoceptor subtype involved in the functional response of a tissue. In aorta, where constitutively active α1D-adrenoeptors are present, the use of different experimental procedures evidenced a complex equilibrium between α1D- and α1A-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