Disease relevance of Gabbr1

• GABA-B receptor activation in the rat globus pallidus potently suppresses pentylenetetrazol-induced tonic seizures [1].
• To determine the involvement of the globus pallidus in mediating epilepsy, the effects of microinjection of a GABA uptake blocker (tiagabine), a benzodiazepine agonist (zolpidem) and a GABA-B receptor agonist (baclofen) on pentylenetetrazol (PTZ)-induced tonic seizure were examined in adult rats [1].
• The inhibition of GABA release by baclofen was abolished by a pretreatment with pertussis toxin (PTX), whereas the inhibition of whole-cell calcium currents by baclofen was only partially depressed by PTX, suggesting that G-protein mechanisms involved in GABAB receptor modulation at the soma and axon terminal may not be identical [2].
• In conclusion, chronic hypertension is associated with an upregulation of GABAB receptor function; however, the tonic activity of the system does not appear to be different between normotensive and hypertensive rats [3].
• Using a validated rat model of absence epilepsy, we have previously found no evidence of abnormal GABAB receptor density or affinity in thalamic tissue [4].

Psychiatry related information on Gabbr1

• Emerging preclinical and clinical data with the metabotropic GABAB receptor agonist baclofen support a role for the modulation of GABAB receptors in the treatment of drug addiction [5].
• The GABAB receptor-positive modulator GS39783 and the GABAB receptor agonist baclofen attenuate the reward-facilitating effects of cocaine: intracranial self-stimulation studies in the rat [5].
• This catatonia may serve as a tool for the study of GABAB receptor function [6].
• Pretreatment in the A10 region with the GABAB agonist baclofen, blocked cocaine-stimulated motor activity in control animals, but not in PTX-pretreated animals, indicating that the PTX treatment had uncoupled the GABAB receptor [7].
• GABAB receptor ligands may well have potential as pharmacotherapies in the treatment of amphetamine abuse and dependence [8].

High impact information on Gabbr1

• Moreover, the GABAB receptor agonist baclofen, and the antagonist 2-hydroxysaclofen had no effect [9].
• We propose to designate the classical site as the GABA A and the novel site as the GABA B receptor [10].
• Direct stimulation of astrocytes, or application of the GABAB-receptor agonist baclofen, potentiated miniature inhibitory postsynaptic currents (mIPSCs) in pyramidal neurons [11].
• The close correlation of the time courses indicates that fast, G protein-mediated depression of voltage-gated calcium channels and thus direct reduction of the presynaptic calcium influx may contribute to the GABAB receptor-induced inhibition of excitatory synaptic transmission in hippocampal neurons in vitro [12].
• We examined the effects of the GABAB receptor agonist baclofen and the mu opioid receptor agonist DAGO on postsynaptic currents evoked by minimal stimulation of inhibitory fibers (meIPSCs) in area CA3 [13].

Chemical compound and disease context of Gabbr1

• RESULTS: Spinal administration of the GABAA receptor antagonist bicuculline or the GABAB receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia in normal rats [14].
• However, GABAB receptor antagonists, such as homotaurine and delta-amino-n-valeric acid, reversed the catatonia induced by baclofen in rats [15].
• OBJECTIVES: Using telemetry recordings, this study examined the interactions between the GABAB receptor agonist baclofen and d-amphetamine, on heart rate responses, body temperature and locomotor activity, and whether these effects could be blocked by the GABAB receptor antagonist SCH 50911 [8].
• In addition, pretreatment of synaptosomes with either the Gi/Go protein inhibitor pertussis toxin or the GABAB receptor agonist baclofen, completely prevented the inhibitory effect of riluzole on 4-aminopyridine-evoked glutamate release [16].
• To investigate GABA-B receptor function in somatotropes, we used rat GH3 adenoma cells, which, like pituitary GH cells, express GABA-B R1 and R2 (as assessed by RT-PCR and immunoelectron microscopy) and produce GABA (checked by high performance liquid chromatography) [17].

Biological context of Gabbr1

• GABA B receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons [18].
• GABAB receptor activation inhibits exocytosis in rat pancreatic beta-cells by G-protein-dependent activation of calcineurin [19].
• Cloning and tissue distribution of novel splice variants of the rat GABAB receptor [20].
• The GABA-B receptor decrease in aged rats seems not to be related to this receptor inhibitory function in penile erection [21].
• We found no GABAB receptor-mediated effect on slow potassium conductance, membrane potential, or input resistance in SCN neurons in vitro using whole-cell patch-clamp recording [2].

Anatomical context of Gabbr1

• The transduction mechanisms underlying presynaptic GABAB receptor-mediated inhibition of transmitter release have been characterized for a variety of synapses in the central nervous system (CNS) [22].
• GABAB receptor transduction mechanisms, and cross-talk between protein kinases A and C, in GABAergic terminals synapsing onto neurons of the rat nucleus basalis of Meynert [22].
• Localization of the GABAB receptor 1a/b subunit relative to glutamatergic synapses in the dorsal cochlear nucleus of the rat [23].
• GABAB-receptor-mediated suppression of sympathetic outflow from the spinal cord of neonatal rats [24].
• A comparison of WIN 55,212-2 (5 microM) with the GABAB receptor agonist baclofen (200 microM) showed that when both drugs were administered independently each produced similar decreases in perforant path paired-pulse potentiation [25].

Associations of Gabbr1 with chemical compounds

• Baclofen, a selective GABAB receptor agonist, reversibly decreased both evoked and spontaneous, miniature, GABAergic inhibitory postsynaptic currents (eIPSCs and mIPSCs, respectively) [22].
• Inhibition of the cAMP/PKA cascade also affected basal GABA release and, in a subset of neurons, occluded the effects of baclofen, suggesting that the GABAB receptor-mediated inhibitory action on GABA release was mediated via decreases in PKA activity [22].
• In contrast, the inducible NO synthase inhibitor L-N(6)-(1-iminoethyl)lysine (20 microg), the GABAB receptor agonist baclofen (0.2 microg), the mixed dopamine receptor antagonist cis-flupenthixol (10 microg), and the oxytocin receptor antagonist d(CH2)5Tyr(Me)-Orn8 -vasotocin (1 microg), were ineffective [26].
• The CB1 antagonists did not affect muscarinic acetylcholine or GABAB receptor signaling [27].
• LTDi was mediated by activation of a presynaptic GABAB receptor, because it was blocked by saclofen and CGP55845 [(2S)-3-{[(15)-1-(3, 4-dichlorophenyl)ethyl]amino-2-hydroxypropyl)(phenylmethyl)phosphinic acid] [28].

Physical interactions of Gabbr1

• The metabotropic GABAB receptor directly interacts with the activating transcription factor 4 [29].
• Inhibition of GABAB receptor binding by guanyl nucleotides [30].

Regulatory relationships of Gabbr1

• These results show that GABAB receptor activation modulates NMDA-stimulated tyrosine hydroxylase activity, further supporting the possibility of a role of GABA in the regulation of striatal dopaminergic neurotransmission [31].

Other interactions of Gabbr1

• GABA-C receptor agonist, cis-4-aminocrotonic acid (CACA, 0.1-1 mM) increased PRL secretion dose-dependently, while GABA-A receptor agonist, 100 microM muscimol, but not GABA-B receptor agonist, 100 microM baclofen, decreased the secretion [32].
• The GABAB receptor agonist (-)-baclofen also diminished the release of SRIF (EC50 = 1.9 microM) and CCK (EC50 = 2.6 microM) [33].
• Consistent with this latter observation, the GABAB receptor agonist, baclofen, dose-dependently increased septal ChAT activity [34].
• Optical determination of presynaptic calcium influx revealed that presynaptic calcium channels were modulated by 2-chloroadenosine (2CA) and baclofen, agonists of the adenosine A1 receptor and the GABAB receptor, respectively [35].
• We have used double-label in situ hybridization techniques to examine the cellular localization of GABAB receptor mRNA in relation to serotonin transporter mRNA and glutamic acid decarboxylase mRNA in the rat dorsal raphe, median raphe and raphe magnus nuclei [36].

Analytical, diagnostic and therapeutic context of Gabbr1

• Tight-seal whole-cell recordings from CA1 pyramidal cells of rodent hippocampus were performed to study GABAB receptor-mediated inhibition of tetrodotoxin (TTX)-resistant IP-SCs [37].
• Focal electrical stimulation produced a hyperpolarizing synaptic potential that was reduced by 75-95% by the GABAB-receptor antagonist 2-hydroxysaclofen (300 microM) [38].
• Micropunches of the NTS were homogenized and reverse transcriptase-polymerase chain reaction was performed to examine mRNA levels for the GABAB receptor [3].
• Microvessels were monitored in in vitro slices using computer-assisted videomicroscopy, and synaptically evoked field responses were simultaneously recorded. gamma-Aminobutyric acid (GABA) and the GABAA receptor agonist, muscimol, elicited vasodilation in hippocampal microvessels, whereas the GABAB receptor agonist, baclofen, elicited constriction [39].
• Quantitative receptor autoradiography was used to assess GABAB receptor binding in three primary subdivisions of the inferior colliculus (IC): dorsal cortex (DCIC), external cortex (ECIC), and the central nucleus (CIC) of 3-, 18-20-, and 26-month-old Fischer 344 rats [40].

References