Effect of Triazine Derivatives on Neuronal NicotinicReceptors

摘要

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.