Figure 4.

Concentration-Effect Curves for Desensitization and Stimulation of ⁸⁶Rb⁺ Efflux by ABT-089. To measure desensitization, thalamic synaptosomes were perfused with the indicated concentrations of ABT-089 for 10 min prior to stimulation by exposure to 10 μM nicotine (○). Each point represents the mean±SEM from three separate experiments. The line was obtained by the non-linear curve fit of the data to the equation: E^a = E₀/(1+A/IC₅₀), where E^a is the ⁸⁶Rb⁺ efflux stimulated with 10 μM nicotine after treatment with [ABT-089]. E₀ is the response to10 μM nicotine without ABT-089 treatment. A is the concentration of ABT-089 to which the samples have been exposed and IC₅₀ is the effective inhibition constant. Stimulation of ⁸⁶Rb⁺ efflux (●) by a 1-min exposure to the indicated concentrations of ABT-089 was determined. Each point represents the mean±SEM from six separate experiments. The line is a fit of the data to the Michaelis-Menten equation. For the desensitization experiments the response elicited by 10 μM nicotine is set at 100%, while for the stimulation experiments the maximal ABT-089 elicited efflux is set at 100%. Maximal efflux rate for ABT-089 was 32±4% that elicited by stimulation with 10 μM nicotine.