Effect of quinine on autoreceptor-regulated serotonin release in the rat hippocampus. 1997

M Y Li, and M E Reith
Department of Biomedical and Therapeutic Sciences, College of Medicine, University of Illinois, Peoria 61656, USA.

The involvement of K+ channels in the autoregulation of terminal serotonin (5-hydroxytryptamine, 5-HT) release was investigated by microdialysis in the hippocampus of conscious rats. Extracellular 5-HT was increased concentration-dependently by the K+ channel blocker quinine (10, 100 and 1000 microM in perfusate), and tetrodotoxin (10 microM) but not fluoxetine (5 microM) exerted a partially attenuating influence. The 5-HT1/2/6 receptor antagonist methiothepin (50 microM) increased dialysate 5-HT, most likely through 5-HT1B autoreceptors tonically activated in the hippocampus of awake rats as opposed to the previously reported lack of effect 5-HT1B autoreceptor blockade in anesthetized rats. The effect of methiothepin was greatly reduced by preperfusion with quinine (100 microM), consonant with a role for quinine-sensitive K+ channels in the autoregulation of 5-HT release in the hippocampus by 5-HT receptor antagonism. In contrast, the reduction in dialysate 5-HT induced by the 5-HT1 receptor agonist RU 24969 (1 microM), in the presence of fluoxetine (5 microM), persisted in the co-presence of quinine, consonant with the involvement of (extrasynaptic?) 5-HT autoreceptors not coupled with quinine-sensitive K+ channels.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008297 Male Males
D008719 Methiothepin A serotonin receptor antagonist in the CENTRAL NERVOUS SYSTEM used as an antipsychotic. Metitepine,Methiothepin Maleate,Methiothepine,Maleate, Methiothepin
D011803 Quinine An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. Biquinate,Legatrim,Myoquin,Quinamm,Quinbisan,Quinbisul,Quindan,Quinimax,Quinine Bisulfate,Quinine Hydrochloride,Quinine Lafran,Quinine Sulfate,Quinine Sulphate,Quinine-Odan,Quinoctal,Quinson,Quinsul,Strema,Surquina,Bisulfate, Quinine,Hydrochloride, Quinine,Sulfate, Quinine,Sulphate, Quinine
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D005473 Fluoxetine The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. Fluoxetin,Fluoxetine Hydrochloride,Lilly-110140,N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine,Prozac,Sarafem,Lilly 110140,Lilly110140
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine

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