title: Effect of triazine derivatives on neuronal nicotinic receptors.
abstract: We have characterized the effect of triazine derivatives on neuronal nicotinic receptors expressed in Xenopus oocytes. All triazines investigated inhibit the current of α7 and α3β4 neuronal nicotinic receptors elicited by acetylcholine. The effect is concentration dependent, reversible, and noncompetitive. In contrast, some derivatives have a dual effect on α4β2 receptors, by potentiating the currents at intermediate concentration and causing inhibition at higher concentrations. Triazine derivatives also affect the macroscopic kinetics of the heteromeric receptors α3β4 and α4β2 accelerating the rise and decay time course of the currents, but have no significant effect on the kinetics of homomeric α7 receptors. Two simple kinetic models are presented. The first reproduces the effects of different concentrations of triazines both on the peak currents and on the macroscopic kinetics of α7 with a simple inhibitory result. The second model describes the behavior of α4β2 receptors involving a more complex dual action.
authors.affiliation: Instituto de Química Avanzada de Cataluña, CSIC , 08034 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vázquez-Romero
authors.forename: Manuel
authors.initials: M
authors.lastname: Criado
authors.forename: Angel
authors.initials: A
authors.lastname: Messeguer
authors.forename: Miquel
authors.initials: M
authors.lastname: Vidal-Mosquera
authors.forename: José
authors.initials: J
authors.lastname: Mulet
authors.forename: Francisco
authors.initials: F
authors.lastname: Sala
authors.forename: Salvador
authors.initials: S
authors.lastname: Sala
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008959:Models, Neurological; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000737:chemistry / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D009865:Oocytes; D018408:Patch-Clamp Techniques; D018009:Receptors, Glycine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000737:chemistry / Q000494:pharmacology; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D018009:Receptors, Glycine; D011978:Receptors, Nicotinic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014227:Triazines; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403530:nicotinic receptor alpha3beta4; C403531:nicotinic receptor alpha4beta2