Quinolinic acid (QUIN) displaced binding of agonist and antagonist ligands for the N-methyl-D-aspartate (NMDA) receptor in rat brain synaptic membranes. Both QUIN and glutamic acid (GLU) potentiated binding of [3H]dizocilpine (MK-801) in the presence of glycine (GLY) alone, whereas the potentiation by QUIN was in a bell-shaped fashion in contrast to that by GLU. However, further addition of spermidine (SPD) induced bell-shaped potentiation by GLU as well as QUIN. The potentiation by QUIN was markedly deteriorated by the further addition of FeCl2 irrespective of the presence of GLY and SPD added. These results suggest that QUIN may potentiate [3H]MK-801 binding to the open NMDA channel in rat brain synaptic membranes through a mechanism different from that underlying the potentiation by GLU.

• MeSH
• 2-amino-5-fosfonovalerát analogy a deriváty   farmakologie   MeSH
• alosterická regulace MeSH
• antagonisté excitačních aminokyselin farmakologie   MeSH
• dizocilpinmaleát metabolismus   MeSH
• glycin farmakologie   MeSH
• inhibiční koncentrace 50 MeSH
• krysa rodu Rattus MeSH
• kyselina chinolinová antagonisté a inhibitory   metabolismus   farmakologie   MeSH
• kyselina glutamová metabolismus   farmakologie   MeSH
• kyselina kynurenová analogy a deriváty   farmakologie   MeSH
• mozek cytologie   metabolismus   MeSH
• potkani Wistar MeSH
• receptory N-methyl-D-aspartátu agonisté   antagonisté a inhibitory   metabolismus   MeSH
• spermidin farmakologie   MeSH
• synaptické membrány metabolismus   MeSH
• vazebná místa MeSH
• železnaté sloučeniny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 2-amino-5-fosfonovalerát MeSH
• 5,7-dichlorokynurenic acid MeSH Prohlížeč
• antagonisté excitačních aminokyselin MeSH
• CGP 39653 MeSH Prohlížeč
• dizocilpinmaleát MeSH
• ferrous chloride MeSH Prohlížeč
• glycin MeSH
• kyselina chinolinová MeSH
• kyselina glutamová MeSH
• kyselina kynurenová MeSH
• receptory N-methyl-D-aspartátu MeSH
• spermidin MeSH
• železnaté sloučeniny MeSH

Postnatal development and properties of N-methyl-d-aspartate (NMDA) receptors were studied with whole-cell and outside-out patch-clamp techniques in interneurons and fluorescence-labelled motoneurons in rat spinal cord slices. Both the absolute amplitude of NMDA-induced currents and currents normalized with respect to the motoneuron capacitance increased significantly at postnatal days 10-13 when compared to the responses evoked at postnatal days 2-3. The mean amplitude of the responses to kainate also increased in motoneurons of postnatal days 10-13. Single-channel currents induced by low concentrations of glutamate, exhibited four distinct amplitude levels corresponding to 19.2 +/- 2.4 pS, 38.4 +/- 3.5 pS, 56.3 +/- 2. 4 pS and 69.6 +/- 3.7 pS. In contrast, the conductance of single channels, recorded under identical conditions, in rat spinal cord interneurons was less, 15.3 +/- 3.2 pS, 29.9 +/- 5.4 pS, 46.7 +/- 4. 8 pS and 62.4 +/- 3.9 pS. The high (56/70 pS) conductance single-channel openings in motoneuron patches were sensitive to NMDA receptor inhibitors D-2-amino-5-phosphonovalerate, 7-chlorokynurenic acid and ifenprodil. Whole-cell NMDA-evoked currents were blocked in a voltage-dependent manner by extracellular Mg2+ with an apparent dissociation constant for Mg2+ binding at 0 mV of 1.8 +/- 0.5 mm. The conductance and relative distribution of NMDA receptor channel openings induced by 1 micrometer glutamate in patches isolated from the motoneurons were independent of age from postnatal day 4 to 14. The results suggest that the properties of NMDA receptor channels in motoneurons differ from those in spinal cord interneurons and cells transfected with NR1/NR2 subunits.

• MeSH
• 2-amino-5-fosfonovalerát farmakologie   MeSH
• agonisté excitačních aminokyselin farmakologie   MeSH
• antagonisté excitačních aminokyselin farmakologie   MeSH
• elektrická vodivost MeSH
• gating iontového kanálu účinky léků   fyziologie   MeSH
• glycin farmakologie   MeSH
• hořčík farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyselina glutamová farmakologie   MeSH
• kyselina kainová farmakologie   MeSH
• kyselina kynurenová analogy a deriváty   farmakologie   MeSH
• metoda terčíkového zámku MeSH
• mícha chemie   cytologie   MeSH
• motorické neurony chemie   účinky léků   MeSH
• N-methylaspartát farmakologie   MeSH
• novorozená zvířata MeSH
• orgánové kultury - kultivační techniky MeSH
• piperidiny farmakologie   MeSH
• potkani Wistar MeSH
• receptory N-methyl-D-aspartátu agonisté   antagonisté a inhibitory   fyziologie   MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-amino-5-fosfonovalerát MeSH
• 7-chlorothiokynurenic acid MeSH Prohlížeč
• agonisté excitačních aminokyselin MeSH
• antagonisté excitačních aminokyselin MeSH
• glycin MeSH
• hořčík MeSH
• ifenprodil MeSH Prohlížeč
• kyselina glutamová MeSH
• kyselina kainová MeSH
• kyselina kynurenová MeSH
• N-methylaspartát MeSH
• piperidiny MeSH
• receptory N-methyl-D-aspartátu MeSH

Spontaneous and N-methyl-D-aspartate (NMDA)-evoked single-channel currents were studied in outside-out patches isolated from cultured rat hippocampal neurons. Both spontaneous and NMDA-evoked single-channel currents reversed at potentials close to 0 mV and exhibited multiple amplitude levels of similar amplitude. Both spontaneous and NMDA-evoked single-channel currents were inhibited by Mg2+ in a voltage-dependent manner and by 7-chlorokynurenic acid. The activity of spontaneous single-channel currents was reduced by the competitive NMDA receptor antagonists, but by one to three orders of magnitude less than expected assuming that the spontaneous activity is due to an ambient NMDA receptor agonist present in the extracellular solution. Our results suggest that, similar to other ligand-gated ion channels, NMDA receptor channels have a dual mode of activation--spontaneous and agonist induced.

• MeSH
• evokované potenciály účinky léků   MeSH
• gating iontového kanálu účinky léků   MeSH
• hipokampus fyziologie   MeSH
• hořčík farmakologie   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• kyselina kynurenová analogy a deriváty   farmakologie   MeSH
• membránové potenciály MeSH
• metoda terčíkového zámku MeSH
• N-methylaspartát farmakologie   MeSH
• neurony fyziologie   MeSH
• novorozená zvířata MeSH
• pravděpodobnostní funkce MeSH
• receptory N-methyl-D-aspartátu fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 7-chlorokynurenic acid MeSH Prohlížeč
• hořčík MeSH
• kyselina kynurenová MeSH
• N-methylaspartát MeSH
• receptory N-methyl-D-aspartátu MeSH

The present study describes the effect of kynurenic (KYNA) and 5,7-dichlorokynurenic (DCKA) acids, acting as selective antagonists at the glycine site on the NMDA receptor complex, upon short-term memory of male rats. Oxiracetam (OXIR) or pramiracetam (PRAM) were used as reference compounds. In the social recognition test, adult animals were injected SC with a drug or vehicle immediately after the first exposure to a juvenile male, 21-24 days old, and reexposed to the same or a novel juvenile 120 min later. Time spent by adults in social investigation of juveniles was measured. Animals treated with KYNA or DCKA (0.3, 3 and 30 mg/kg in both cases) and OXIR (30 and 60 mg/kg) had significantly reduced investigation time when reexposed to the same juvenile as compared to controls. No reduction of investigation time was found in those drugged animals reexposed to a novel juvenile. The findings suggest that KYNA and DCKA improved retention of memory for olfactory stimuli in adult male rats. In the object recognition test, the duration of exploration of two identical objects during the sample trial and the familiar and a new object during the choice trial, performed 60 min later, was evaluated. Drugs or vehicles were administered SC 30 min prior to the sample trial. On choice one, animals treated with KYNA or DCKA (0.6 and 30 mg/kg in both cases) and PRAM (30 mg/kg) spent more time in exploring a new object than the familiar one as compared to controls. This suggests that the drugged animals were able to remember the familiar object.(ABSTRACT TRUNCATED AT 250 WORDS)

• MeSH
• antagonisté excitačních aminokyselin farmakologie   MeSH
• časové faktory MeSH
• habituace (psychofyziologie) účinky léků   MeSH
• krátkodobá paměť účinky léků   MeSH
• krysa rodu Rattus MeSH
• kyselina kynurenová analogy a deriváty   farmakologie   MeSH
• potkani Wistar MeSH
• sociální identifikace * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 5,7-dichlorokynurenic acid MeSH Prohlížeč
• antagonisté excitačních aminokyselin MeSH
• kyselina kynurenová MeSH