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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Adenosine, by acting on adenosine A1 and A2A receptors, exerts opposite modulatory roles on striatal extracellular levels of glutamate and dopamine, with activation of A1 inhibiting and activation of A2A receptors stimulating glutamate and dopamine release. Adenosine-mediated modulation of striatal dopaminergic neurotransmission could be secondary to changes in glutamate neurotransmission, in view of evidence for a preferential colocalization of A1 and A2A receptors in glutamatergic nerve terminals. By using in vivo microdialysis techniques, local perfusion of NMDA (3, 10 µm), the selective A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS 21680; 3, 10 µm), the selective A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 300, 1000 µm), or the non-selective A1-A2A receptor antagonist in vitro caffeine (300, 1000 µm) elicited significant increases in extracellular levels of dopamine in the shell of the nucleus accumbens (NAc). Significant glutamate release was also observed with local perfusion of CGS 21680, CPT and caffeine, but not NMDA. Co-perfusion with the competitive NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid (APV; 100 µm) counteracted dopamine release induced by NMDA, CGS 21680, CPT and caffeine. Co-perfusion with the selective A2A receptor antagonist MSX-3 (1 µm) counteracted dopamine and glutamate release induced by CGS 21680, CPT and caffeine and did not modify dopamine release induced by NMDA. These results indicate that modulation of dopamine release in the shell of the NAc by A1 and A2A receptors is mostly secondary to their opposite modulatory role on glutamatergic neurotransmission and depends on stimulation of NMDA receptors. Furthermore, these results underscore the role of A1 vs. A2A receptor antagonism in the central effects of caffeine.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies have demonstrated opposing roles for adenosine A1 and A2A receptors in the modulation of extracellular levels of glutamate and dopamine in the striatum. In the present study, acute systemic administration of motor-activating doses of the A2A receptor antagonist MSX-3 significantly decreased extracellular levels of dopamine and glutamate in the shell of the rat nucleus accumbens (NAc) and counteracted both dopamine and glutamate release induced by systemic administration of motor-activating doses of either the A1 receptor antagonist CPT or caffeine. Furthermore, exposure to caffeine in the drinking water (1 mg/mL, 14 days) resulted in tolerance to the effects of systemic injection of CPT or caffeine, but not MSX-3, on extracellular levels of dopamine and glutamate in the NAc shell. The present results show: first, the existence of opposite tonic effects of adenosine on extracellular levels of dopamine and glutamate in the shell of the NAc mediated by A1 and A2A receptors; second, that complete tolerance to caffeine's dopamine- and glutamate-releasing effects which develops after chronic caffeine exposure is attributable to an A1 receptor-mediated mechanism. Development of tolerance to the dopamine-releasing effects of caffeine in the shell of the NAc may explain its weak addictive properties and atypical psychostimulant profile.
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  • 3
    ISSN: 0044-2313
    Keywords: Silicon Compounds ; Diaminosilylene ; Spirosilanes ; Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Silicon Compounds with Strong Intramolecular Steric Interactions. 54Mitteilung 53: K. Peters, E.-M. Peters, H. G. von Schnering, H. Piel, M. Weidenbruch, Z. Kristallogr., im Druck. . Attempted Generation of a Diaminosilylene: Formation of Spirosilanes and of Related CompoundsTreatment of the bulky substituted N,N′-bis(2,6-dimethylphenyl)ethylenediamine with n-butyllithium and subsequent cyclization with trichlorosilane or silicon tetrachloride gives the 2-chloro- and 2,2-dichloro-1,3-diaza-2-silacyclopentanes 3 and 4, respectively. Both compounds can easily be converted into the azido- (5) and diazidosilanes (6) and into the trisilane 7. Chlorine elimination from 4 in the presence of 2,3-dimethylbutadiene leads to the spirosilane 9 containing a nine-membered ring, whose structure was confirmed by X-ray crystallography. Reaction of 4 with lithium, followed by treatment with isopropanol gives beside other products the compound 10 consisting of two diazasilacyclopentane rings linked by a bridging ethylenediamino group. The X-ray structure determination of 10 shows that all six nitrogen atoms have a nearly planar environment. Upon photolysis, the azidosilane 5 provides the disiladispiro compound 12, presumably via a silanimine intermediate.
    Notes: Umsetzung von sperrig substituiertem N,N′-Bis(2,6-dimethylphenyl)ethylendiamin mit n-Butyllithium und nachfolgende Cyclisierung mit Trichlorsilan oder Siliciumtetrachlorid ergibt die 2-Chlor- und 2,2-Dichlor-1,3-diaza-2-silacyclopentan-Derivate 3 und 4. Beide Verbindungen können leicht in die Azido- (5) und Diazidosilane (6) sowie in das Trisilan 7 übergeführt werden. Die Chloreliminierung aus 4 in Gegenwart von 2,3-Dimethylbutadien liefert das Spirosilan 9 mit einem neungliedrigen Ring, dessen Aufbau durch die Röntgenstrukturanalyse gesichert ist. Umsetzung von 4 mit Lithium, gefolgt von der Einwirkung von Isopropanol führt neben anderen Produkten zu der Verbindung 10, in der zwei Diazasilacyclopentanringe durch eine Ethylendiaminbrücke miteinander verknüpft sind. Die Röntgenstrukturanalyse von 10 belegt die fast planare Umgebung aller sechs Stickstoffatome. Durch Photolyse von 5 wird vermutlich über ein intermediäres Silanimin die Disiladispiro-Verbindung 12 erhalten.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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