Modulation of the Electrically Evoked Release of 5‐[³H]Hydroxytryptamine from Rat Cerebral Cortex: Effects of Alpidem, CL 218872, and Diazepam

Abstract

The effect of omega (benzodiazepine)-receptor agonists, antagonists, and inverse agonists on the electrically evoked release of 5-[3H]hydroxytryptamine ([3H]5-HT) was studied in superfused slices of the rat frontal cerebral cortex. The electrically evoked release of [3H]5-HT was enhanced by nanomolar concentrations of diazepam and the selective omega 1-receptor agonists alpidem and CL 218872. The omega 1/omega 2- and omega 1-receptor antagonists flumazenil and CGS 8216, respectively, did not modify the electrically evoked release of [3H]5-HT. The omega 3-receptor agonist Ro 5-4864 and the omega 1-receptor inverse agonist ethyl-beta-carboline-3-carboxylate on their own did not affect the electrically evoked release of [3H]5-HT. On the other hand, the inverse agonist 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methyl ester (DMCM), at micromolar concentrations, inhibited both the spontaneous and the evoked release of [3H]5-HT. The facilitation of the electrically evoked release of [3H]5-HT by diazepam, alpidem, or CL 218872 was potentiated by gamma-aminobutyric acid (GABA). Exposure to flumazenil and CGS 8216 antagonized the facilitation by diazepam, alpidem, or CL 218872 of [3H]5-HT release. The inhibition of the release of [3H]5-HT by DMCM was not modified by exposure to either flumazenil, CGS 8216, or GABA. The inhibitory effect of DMCM was not observed when monoamine oxidase activity was inhibited by pargyline.(ABSTRACT TRUNCATED AT 250 WORDS)

Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation

“…Peak areas and area ratios were calculated within Skyline. 33 Raw files were loaded into Skyline files containing target proteins/peptides/transitions. All individual SRM transitions and integration areas were manually inspected.…”

Functional characterization of a 5‐HT3 receptor which modulates the release of 5‐HT in the guinea‐pig brain

“…Previous studies have documented the capacity of various types of presynaptic receptors to modulate 5-HT release, such as the benzodiazepine type 1 receptor (Lista et al, 1988), and also interactions between receptors demonstrated to be located on the same nerve terminals, such as between the a2-adrenoceptor and the 5-HT autoreceptor (Blier et al, 1990). In the present study, the blockade of 5-HT3 receptors with ICS 205-930 did not alter the differential effectiveness of an agonist of the terminal 5-HTlD autoreceptor in attenuating the release of [3H]-5-HT at two frequencies of stimulation.…”

The benzodiazepine receptor inverse agonist DMCM decreases serotonergic transmission in rat hippocampus: An in viovo electrophysiological study

“…Behavioral, electrophysiological, and biochemical data indicate that y-aminobutyric acid (GABAA)-benzodiazepine receptors (GAE3AABZR) can modulate the function of serotonergic (5-HT) neurons (Iversen, 1984). Recent in vitro (Lista et al, 1988) and in vivo (Lista et al, 1989a, b) data suggest that GABAAIBZRmodulate 5-HT release in several regions of the rat central nervous system. In the rat frontal cortex, benzodiazepine agonists enhance L3H15-HT release, but the BZR inverse agonist P-CCE (ethyl-~-carboline-3-carboxilate) modifies neither the release of [3H]5-HT (Lista et al, 1988) nor the diazepam-induced facilitation of [,H]5-HT release (Lista et al unpublished observations).…”

“…Recent in vitro (Lista et al, 1988) and in vivo (Lista et al, 1989a, b) data suggest that GABAAIBZRmodulate 5-HT release in several regions of the rat central nervous system. In the rat frontal cortex, benzodiazepine agonists enhance L3H15-HT release, but the BZR inverse agonist P-CCE (ethyl-~-carboline-3-carboxilate) modifies neither the release of [3H]5-HT (Lista et al, 1988) nor the diazepam-induced facilitation of [,H]5-HT release (Lista et al unpublished observations). This suggests that GABAABZR linked to presynaptic modulation of 5-HT release in frontal cortex are devoid of an inverse agonist binding site.…”

“…DMCM (6,7-dimethoxy-4-ethyl-~-carboline-3-carboxylic acid methyl ester), is another inverse agonist of BZR 9 nM; Braestrup et al, 1983), which has the peculiarity of being also a monoamine oxidase inhibitor (MAOI; 1C5,,: 47 M, Y. Claustre, personal communicathe release of [,H]5-HT, but this effect appeared not to involve BZR, but rather seemed due to its MAOI activity (Lista et al, 1988). Indeed, inhibition of MA0 in super-tion).…”