THE ROLE OF INTRANEURONAL 5-HT AND OF TRYPTOPHAN HYDROXYLASE ACTIVATION IN THE CONTROL OF 5-HT SYNTHESIS IN RAT BRAIN SLICES INCUBATED IN K+-ENRICHED MEDIUM

1. Protoveratrine A increased the release of gamma-amino[3H]butyrate from small slices of rat cerebral cortex. This effect increased with increasing protoveratrine concentration, reaching a maximum at 100 microM. 2. Removal of Ca2+ from the superfusing medium did not change the increase in release due to 10 microM-protoveratrine; however, the Ca2+ antagonists, compound D-600, La3+, Mn2+, Mg2+ and also high Ca2+ concentration inhibited the effect of the alkaloid, as did procaine. 3. Protoveratrine A increased the uptake of 22Na+ into the slices with a similar dose-response curve to that found for gamma-aminobutyrate release. For the most part, the substances that inhibited protoveratrine-stimulated gamma-aminobutyrate release also inhibited 22Na+ uptake, although the correlation was not perfect. 4. Although extracellular Ca2+ is not required for protoveratrine-induced gamma-aminobutyrate release, an increase in Na+ influx that is susceptible to inhibition by some Ca2+ antagonists does appear to be associated with this phenomenon. However, the possibility remains that changes in the free intracellular Ca2+ concentration may be important for transmitter release induced by depolarizing veratrum alkaloids.

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Na+ influx-induced decrease of (Na++ K+) -ATPase activity in rat brain slices: role of Ca2+

European Journal of Pharmacology ◽

10.1016/0014-2999(91)90850-p ◽

1991 ◽

Vol 204 (3) ◽

pp. 257-263 ◽

Cited By ~ 5

Author(s):

Matsuda Toshio ◽

Shimizu Isao ◽

Baba Akemichi

Keyword(s):

Atpase Activity ◽

Rat Brain ◽

Brain Slices

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Role of the Hyperpolarization‐Activated Cation Current ( I h ) in Pacemaker Activity in Area Postrema Neurons of Rat Brain Slices

The Journal of Physiology ◽

10.1113/jphysiol.2003.047191 ◽

2003 ◽

Vol 552 (1) ◽

pp. 135-148 ◽

Cited By ~ 39

Author(s):

Makoto Funahashi ◽

Yoshihiro Mitoh ◽

Atsushi Kohjitani ◽

Ryuji Matsuo

Keyword(s):

Rat Brain ◽

Area Postrema ◽

Brain Slices ◽

Pacemaker Activity ◽

Cation Current

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The role of brain M1 receptor in learning and memory in mice and the aging of the receptor-mediated phosphatidylinositol (PI) turnover in rat brain slices

Neuroscience Research Supplements ◽

10.1016/0921-8696(90)90065-b ◽

1990 ◽

Vol 15 ◽

pp. S11

Author(s):

Toshio Ohnuki ◽

Yasuyuki Nomura

Keyword(s):

Rat Brain ◽

Learning And Memory ◽

Brain Slices ◽

Pi Turnover ◽

M1 Receptor

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Studies on the role of Na+, K+ and Cl? ion permeabilities in K+-induced release of 3H-noradrenaline from rat brain slices and synaptosomes and in its presynaptic ?-adrenergic modulation

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/bf00500063 ◽

1981 ◽

Vol 317 (2) ◽

pp. 103-109 ◽

Cited By ~ 21

Author(s):

Johan Wemer ◽

Anton N. M. Schoffelmeer ◽

Arie H. Mulder

Keyword(s):

Rat Brain ◽

Brain Slices ◽

Adrenergic Modulation

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Regulation of cerebral kynurenine and 5-hydroxyindole pathways during tryptophan loading

Cephalalgia ◽

10.1177/03331024830030s121 ◽

1983 ◽

Vol 3 (1_suppl) ◽

pp. 139-142 ◽

Cited By ~ 2

Author(s):

Victor Rizza ◽

Ennio Bousquet ◽

Franco Guerrera ◽

Massimo De Regis

Keyword(s):

Superoxide Dismutase ◽

Nous Avons ◽

Rat Brain ◽

Inverse Relationship ◽

Tryptophan Hydroxylase ◽

Brain Slices ◽

Tryptophan Concentration ◽

Reducing Environment ◽

Dose Dependent Increase ◽

Dose Dependent

Cerebral tryptophan metabolism was studied in rat brain slices. The results show that serotonin production was inhibited at high levels of tryptophan or 5-oxo-l-prolyltryptophan. In contrast, kynurenine formation showed a dose dependent increase at the various concentrations of tryptophan or 5-oxo-l-prolyltryptophan. Measurements of the activities of tryptophan hydroxylase (TH) and indoleamine 2,3-dioxygenase (IDOase) in crude brain homogenates showed that serotonin formation was linear in the presence of dithiothreitol, whereas kynurenine production was inhibited in the presence of diothiothreitol or superoxide dismutase. These results suggest an inverse relationship in the regulation of 5-hydroxyindole and kynurenine pathways. The former being inhibited in the presence of high tryptophan concentration while the latter is enhanced. Furthermore, a high intracellular thiol-disulphide ratio appears to favour serotonin formation, whereas a highly reducing environment decreases kynurenine production. Nous avons étudié le métabolisme du Trp au mayer de sections de tissu cérébral de rat. Nos résultats montrent que la production de 5-HT est inhibie à hautes concentrations de Trp ou de 5-oxo-l-prolyltryptophane. Au contraire, la production de Kynurenine augmente par rapport à ces concentrations. L'évaluation de l'activité de la TH et de la IDO ase démontre que la production de 5-HT augmente de façon linéaire en presence de di-thio-theréitole tandis que la production de Kinurénine ed inhibite en présence de di-thio-thréitole on super-oxide dismuntase. Ces résultats suggérent une relation inverse dous la régulation du métabolisme du 5-hydroxi-indole er de la Kynurénine: le premier est inhibie en presence de hautes concentrations de Trp tandis que la deuxiéme est stimulée. En ontre, un haut rapport intracellular thide-disulphide semble favoriser la production de 5-HT tandis que une ambiance fort réduisant abaisse la production de Kynurénine. Abbiamo studiato il metabolismo del Trp in sezioni di tessuto cerebrale di ratto. Dai risultati emerge che la produzione di 5-HT viene inibita da alte concentrazioni di Trp o di 5-oxo-l-proliltriptofano. Viceversa la produzione di Kynurenina mostra un incremento dose-dipendente. La valutazione dell-attività della TH e della IDO asi dimostra che la produzione di 5-HT aumenta linearmente in presenza di ditiotreitolo mentre la produzione di Kynurenina viene inibita in presenza di ditiotreitolo o superossido dismutasi. Questi risultati suggeriscono una relazione inversa nella regolazione delle vie metaboliche del 5-idrossi-indolo e della Kynurenina: la prima viene inibita in presenza di alte concentrazioni di Trp, mentre la seconda è potenziata. Inoltre, un alto rapporto intracellulare tiolo-disulfide sembra favorire la produzione di 5-HT mentre un ambiente fortemente riducente abbassa la produzione di Kynurenina.

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