Facilitation of 5-hydroxytryptamine3 receptor desensitization by fluoxetine.
Effect of fluoxetine on the desensitization of the inward current mediated by 5-hydroxytryptamine3 receptors in rat nodose ganglion neurons was investigated with whole cell patch-clamp recording. 5-Hydroxytryptamine3 current desensitization was best fitted in most experiments by a single exponential function and showed little dependence on membrane potential. Fluoxetine greatly facilitated the rate of 5-hydroxytryptamine3 current desensitization in a dose-dependent manner. The effect of fluoxetine was gradual, long-lasting, voltage-independent and the recovery was incomplete. The IC50 value for the decrease of the desensitization time-constant by fluoxetine was 0.171 microM and the Hill coefficient was 1.1. Fluoxetine also inhibited the peak and steady-state 5-hydroxytryptamine3 current with the latter being more sensitive to fluoxetine. The IC50 value for the effect of fluoxetine on peak current was 1.27 microM and that on steady-state current was 0.172 microM. There is a highly significant correlation between the two effects of fluoxetine on current desensitization and on current amplitudes: r-values for the correlation between the decrease in time-constant and the reduction in peak and steady-state current amplitudes were 0.82 and 0.88, respectively (P < 0.001). This action of fluoxetine on 5-hydroxytryptamine3 receptors may be involved in the behavioral effects of fluoxetine.
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Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009620:Nodose Ganglion / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors; D014326:Tropanes / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D005473:Fluoxetine; D012701:Serotonin; C042253:bemesetron