title: Functional characterization of alpha 1-adrenoceptor subtypes in vascular tissues using different experimental approaches: a comparative study.
abstract: 1. The alpha(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 (alpha(1A) selective) and BMY 7378 (alpha(1D) selective) have been used in different experimental procedures. 2. 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%). 3. 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. 4. The CICa was the simplest method to characterize the predominant alpha(1)-adrenoceptor subtype involved in the functional response of a tissue. 5. In aorta, where constitutively active alpha(1D)-adrenoeptors are present, the use of different experimental procedures evidenced a complex equilibrium between alpha(1D)- and alpha(1A)-adrenoceptor subtypes. 6. 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.
authors.affiliation: Departament de Farmacologia, Facultat de Farmacia, Universitat de València, Avda, Vincent Andres Estelles s/n 46100, Burjassot, Valencia, Spain.
authors.forename: Regina
authors.initials: R
authors.lastname: Gisbert
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Madrero
authors.forename: Valentina
authors.initials: V
authors.lastname: Sabino
authors.forename: M Antonia
authors.initials: MA
authors.lastname: Noguera
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Ivorra
authors.forename: Pilar
authors.initials: P
authors.lastname: D'Ocon
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013623:Tail / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1