title: Relationship between alpha-adrenoceptor occupancy and contractile response in rat vas deferens. Experimental and theoretical analysis.
abstract: The rat vas deferens has been considered to be the tissue of choice to study alpha-adrenergic drugs. However, some of these agonists have elicited complex responses in this organ. Therefore, detailed characterization of alpha-adrenoceptor-mediated responses of the rat vas deferens was the aim of this work. Experiments were designed to study the contractile response of this tissue to phenylethanolamine (noradrenaline) and to two imidazolines (oxymetazoline and naphazoline). These responses were related to receptor occupancy and to other parameters of drug action, i.e. dissociation constants, relative efficacies, ED50 and maximal responses. A theoretical model was used to check the experimental data. There was a non-linear relationship between response and receptor occupancy with all three agonists. The dissociation constants for noradrenaline, oxymetazoline and naphazoline were 11.06, 0.15 and 0.10 microM, respectively. The rat vas deferens had 75-80% spare receptors for noradrenaline. Oxymetazoline and naphazoline were shown to be partial agonists with low relative efficacies as compared to noradrenaline (0.0063 and 0.0056 respectively). The dose-response curves generated by the model for partial agonists were similar to the curves obtained experimentally in vitro.
authors.affiliation: Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas y de Recursos Naturales, Universidad de Concepción, Chile.
authors.forename: A
authors.initials: A
authors.lastname: Díaz-Toledo
authors.forename: M C
authors.initials: MC
authors.lastname: Martí
mesh_terms: D000818:Animals; D003983:Dibenzylchlorethamine / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009278:Naphazoline / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D010109:Oxymetazoline / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology*
chemical_list: D011942:Receptors, Adrenergic, alpha; D003983:Dibenzylchlorethamine; D010109:Oxymetazoline; D009278:Naphazoline; D009638:Norepinephrine