• MeSH
• baklofen farmakologie   terapeutické užití   MeSH
• centrální nervový systém fyziologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• GABA MeSH
• imunohistochemie metody   MeSH
• molekulární struktura MeSH
• neurotransmiterové látky MeSH
• receptory GABA-B dějiny   farmakologie   fyziologie   MeSH
• Publikační typ
• přehledy MeSH
• srovnávací studie MeSH

• MeSH
• finanční podpora výzkumu jako téma MeSH
• glutamátové receptory fyziologie   chemie   MeSH
• nervový přenos genetika   MeSH
• receptory GABA fyziologie   chemie   MeSH
• receptory metabotropního glutamátu agonisté   antagonisté a inhibitory   chemie   MeSH
• synapse fyziologie   chemie   MeSH
• techniky in vitro MeSH

Our data indicate the significant intrinsic efficacy of GABA(B)-receptors in rat brain cortex already at birth (PD1, PD2). Subsequently, baclofen- and SKF97541-stimulated G-protein activity, measured by agonist-stimulated, high-affinity [(35)S]GTPgammaS binding assay, was increased; the highest level of both baclofen and SKF97541-stimulated [(35)S]GTPgammaS binding was detected between PD10 and PD15. In older rats, baclofen- and SKF97541-stimulated [(35)S]GTPgammaS binding was continuously decreased so, that the level in adult, 90-days old animals, was not different from that in newborn animals. The potency of G-protein response to baclofen (characterized by EC(50) values) was also high at birth but unchanged by further postnatal development. An individual variance among different agonists was observed in this respect as the potency of SKF97541 response was decreased between the birth and adulthood. Accordingly, the highest plasma membrane density of GABA(B)-R, determined by saturation binding assay with antagonist [(3)H]CGP54626, was measured in 1-day old animals (2.27+/-0.08 pmol · mg(-1)). The further development was reflected in a decrease of [(3)H]CGP54626 binding as the B(max) values of 1.38+/-0.05 and 0.93+/-0.04 pmol · mg(-1) were determined in PM isolated from 13- and 90-days old rats, respectively.

• MeSH
• agonisté receptorů GABA-B farmakologie   MeSH
• baklofen farmakologie   MeSH
• buněčná membrána účinky léků   metabolismus   MeSH
• časové faktory MeSH
• krysa rodu rattus MeSH
• mozková kůra růst a vývoj   metabolismus   MeSH
• novorozená zvířata MeSH
• organofosforové sloučeniny farmakologie   MeSH
• receptory GABA-B metabolismus   MeSH
• signální transdukce * MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• antagonisté receptorů GABA-A MeSH
• antagonisté receptorů GABA-B MeSH
• bikukulin aplikace a dávkování   MeSH
• epilepsie patofyziologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• GABA antagonisté terapeutické užití   MeSH
• krysa rodu rattus MeSH
• organofosforové sloučeniny aplikace a dávkování   MeSH
• receptory GABA-A účinky léků   MeSH
• receptory GABA-B účinky léků   MeSH
• záchvaty patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

Cortical epileptic foci elicited by local application of bicuculline methiodide represent a model of interictal epileptic activity with a transition into ictal phases. We studied a role of GABA-B receptors in this model using GABA-B receptor antagonist CGP35348 in adult rats with implanted cortical electrodes and cannula. CGP35348 (100 or 200 mg/kg i.p.) did not affect interictal discharges but it augmented ictal activity. Latency to the first ictal episode was decreased by the lower dose of CGP35348, duration of episodes was increased by the higher dose. GABA-B receptor antagonist did not influence purely cortical epileptic phenomenon but it is proconvulsant in ictal activity generated with participation of subcortical structures.

• MeSH
• antagonisté receptorů GABA-B toxicita   MeSH
• bikukulin analogy a deriváty   MeSH
• časové faktory MeSH
• elektroencefalografie MeSH
• epilepsie chemicky indukované   metabolismus   patofyziologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• mozková kůra metabolismus   patofyziologie   účinky léků   MeSH
• mozkové vlny účinky léků   MeSH
• organofosforové sloučeniny toxicita   MeSH
• potkani Wistar MeSH
• reakční čas účinky léků   MeSH
• receptory GABA-B metabolismus   účinky léků   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

Funkční charakteristika uspořádání BR1 a BR2 proteinů v rámci GABA-B receptorů.Hlavním tématem je identifikace částí obou proteinů, které se navzájem dotýkají či přitahují. Tyto identifikované interakce budou dále zkoumány pomocí molekulární metodologie.Tato DNA rekombinantní technologie nám slouží jako prostředek k tvorbě proteinů s požadovanými modifikacemi sekvence.; The aim of our studies is to map portions of the BR1 and BR2 proteins that are in close proximity and contribute to the protein-protein interactions that are involvolved in the structural formation of the functional GABA-B receptors. Information about the proximity of certain portains of proteins will be used as clues in protein modeling and will provide more information about the structure-function relatioship of GABA-B receptors.

• MeSH
• exprese genu MeSH
• receptory GABA-B MeSH
• receptory spřažené s G-proteiny MeSH
• rekombinantní DNA MeSH
• transformace genetická MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biologie
• neurologie
• psychiatrie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

GABA-B receptor agonist SKF97541 exhibits age-dependent anticonvulsant and proconvulsant actions in developing rats. It suppressed tonic phase of generalized seizures induced by pentetrazol in 7-, 12- and 18-day-old rats and increased their latency in 7- and 12-day-old animals. Other results in 18-day-old animals are not so clear. SKF97541 blocked the appearance of minimal clonic seizures, but tended to decrease latencies of both types of seizures. In addition, it significantly decreases latency of generalized seizures in adult rats. The mixed effects of SKF97541 are in agreement with those of baclofen but there are substantial differences between the actions of these two agonists in individual age groups.

• Klíčová slova
• GABA-B receptor, Agonist, Convulsions, Ontogeny, Rat,
• MeSH
• agonisté receptorů GABA-B MeSH
• antikonvulziva farmakologie   MeSH
• baklofen farmakologie   MeSH
• financování organizované MeSH
• GABA agonisté farmakologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• organofosforové sloučeniny farmakologie   MeSH
• pentylentetrazol MeSH
• potkani Wistar MeSH
• reakční čas účinky léků   MeSH
• receptory GABA-B metabolismus   MeSH
• věkové faktory MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• záchvaty chemicky indukované   metabolismus   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

GABA(B) receptors (GABA(B)Rs) regulate the excitability of most neurons in the central nervous system by modulating the activity of enzymes and ion channels. In the sustained presence of the neurotransmitter γ-aminobutyric acid, GABA(B)Rs exhibit a time-dependent decrease in the receptor response-a phenomenon referred to as homologous desensitization. Desensitization prevents excessive receptor influences on neuronal activity. Much work focused on the mechanisms of GABA(B)R desensitization that operate at the receptor and control receptor expression at the plasma membrane. Over the past few years, it became apparent that GABA(B)Rs additionally evolved mechanisms for faster desensitization. These mechanisms operate at the G protein rather than at the receptor and inhibit G protein signaling within seconds of agonist exposure. The mechanisms for fast desensitization are ideally suited to regulate receptor-activated ion channel responses, which influence neuronal activity on a faster timescale than effector enzymes. Here, we provide an update on the mechanisms for fast desensitization of GABA(B)R responses and discuss physiological and pathophysiological implications.

• MeSH
• buněčná membrána metabolismus   MeSH
• časové faktory MeSH
• GABA metabolismus   MeSH
• lidé MeSH
• neurony metabolismus   MeSH
• proteiny vázající GTP metabolismus   MeSH
• receptory GABA-B metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Activation of GABA(B) receptors leads to longer inhibitory postsynaptic potentials than activation of GABA(A) receptors. Therefore GABA(B) receptors may be a target for anticonvulsant therapy. The present study examined possible effects of GABA(B) receptor agonist SKF97541 on cortical and hippocampal epileptic afterdischarges (ADs). Epileptic ADs elicited by electrical stimulation of sensorimotor cortex or dorsal hippocampus were studied in adult male Wistar rats. Stimulation series were applied 6 times with 10- or 20-min interval. Either interval was efficient for reliable elicitation of cortical ADs but stimulation at 10-min intervals did not reliably elicit hippocampal ADs, many stimulations were without effect. SKF97541 in dose 1 mg/kg significantly prolonged cortical ADs. Duration of hippocampal ADs was not significantly changed by either dose of SKF97541 in spite of a marked myorelaxant effect of the higher dose. Our present data demonstrated that neither cortical nor hippocampal ADs in adult rats were suppressed by GABA(B) receptor agonist SKF97541. Proconvulsant effect on cortical ADs indicates a different role in these two brain structures. In addition, duration of refractory period for electrically-induced ADs in these two structures in adult rats is different.

• MeSH
• agonisté receptorů GABA-B farmakologie   MeSH
• elektroencefalografie účinky léků   MeSH
• epilepsie patofyziologie   MeSH
• hipokampus patofyziologie   MeSH
• krysa rodu rattus MeSH
• mozková kůra patofyziologie   MeSH
• organofosforové sloučeniny farmakologie   MeSH
• potkani Wistar MeSH
• pyramidové buňky účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Inhibition mediated by GABA-B receptors can play a role in epilepsy. We therefore studied its involvement in cortical epileptic afterdischarges in adult rats by means of a GABA-B receptor agonist baclofen. Three different experiments were performed with cortical epileptic afterdischarges and an additional experiment studied possible effect of baclofen on cortical interhemispheric (transcallosal) evoked potentials. Baclofen was administered intraperitoneally in doses of 3 or 6 mg/kg. In contrast to a marked proconvulsant action of a GABA-B receptor antagonist baclofen did not exhibit clear anticonvulsant action against EEG afterdischarges but a moderate effect on motor phenomena was observed. On the contrary, it tended to decrease threshold intensities for individual epileptic phenomena. Augmentation of postictal refractoriness by baclofen was found only with a short poststimulation interval (2 min). Cortical interhemispheric responses induced by single pulses were influenced only moderately by baclofen; paired-pulse potentiation induced by short intervals between stimuli was not changed but there was a depression of the second response induced 200 and 250 ms after the first one with the 6 mg/kg dose of baclofen. Failure of baclofen to exhibit an expected anticonvulsant activity might be due to a complexity of GABA-B inhibitory system (pre- as well as postsynaptic localization of GABA-B receptors).

• MeSH
• baklofen farmakologie   terapeutické užití   MeSH
• financování organizované MeSH
• GABA agonisté farmakologie   terapeutické užití   MeSH
• krysa rodu rattus MeSH
• mozková kůra účinky léků   patofyziologie   MeSH
• neúspěšná terapie MeSH
• receptory GABA-B účinky léků   MeSH
• stupeň závažnosti nemoci MeSH
• záchvaty farmakoterapie   patofyziologie   MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH