gaba b type receptor antagonist  (Tocris)

Journal: Signal Transduction and Targeted Therapy

Article Title: Endothelial GABA protects against aortic dissection by inhibiting endothelial and mitochondrial dysfunction and maintaining vascular homeostasis

doi: 10.1038/s41392-026-02619-2

Figure Lengend Snippet: GABA maintains homeostatic mitochondrial levels in the context of oxidative stress. a , b Representative images and quantification of western blots of ICAM-1, P-p42, total-p42, and c-FOS expression in HAECs treated with GABA or GABA + CGP52432 (one-way ANOVA, mean ± S.D.; n = 4). c Representative morphology of the mitochondrial network structure as assayed by MitoTracker Red staining in HAECs treated with GABA alone or in combination with CGP52432 . d , e Mitochondrial ROS production in HAECs treated with GABA alone or in combination with CGP52432 (one-way ANOVA, mean ± S.D.; n = 3). Scale bar = 10 μm. f Intercellular ATP synthesis in H 2 O 2 -induced HAECs treated with GABA alone or in combination with CGP52432 (one-way ANOVA, mean ± S.D.; n = 3). g The impact of GABA on oxidative phosphorylation and glycolytic rates in H 2 O 2 -induced HAECs. h Western blotting of GABBR2 accumulation in mitochondria with GABA regulation according to different time spans. i Western blotting of GABBR2 accumulation in mitochondria in the GABA- or CGP52432 -treated groups. j , k Representative images and quantification of the correlations of GABBR2 and mitochondria with GABA alone or in combination with CGP52432 (one-way ANOVA, mean ± S.D.). Scale bar = 5 μm

Article Snippet: The GABA B receptor antagonist CGP52432 (MCE, USA; catalog: HY-103531; intravenous injection once daily, 10 mg/kg/dose) was administered.

Techniques: Western Blot, Expressing, Staining, Phospho-proteomics

Journal: Signal Transduction and Targeted Therapy

Article Title: Endothelial GABA protects against aortic dissection by inhibiting endothelial and mitochondrial dysfunction and maintaining vascular homeostasis

doi: 10.1038/s41392-026-02619-2

Figure Lengend Snippet: Endothelial cell-derived GABA protects smooth muscle cell homeostasis from inflammatory stimulation. a Representative images and quantification of western blot showing the protein expression of MMP-2 and MMP-9 in IL-1b-induced SMCs treated with GABA alone or in combination with CGP52432 (one-way ANOVA, mean ± S.D.; n = 3). b qRT‒PCR analysis of the mRNA expression of MMP-2 and MMP-9 in IL-1b-induced SMCs treated with GABA alone or in combination with CGP52432 (one-way ANOVA, mean ± S.D.; n = 3). c The differentially expressed proteins in IL-1b-induced SMCs with and without GABA treatment are shown as volcano plots. d Heatmap analysis indicates that Notch3 participates in this process. e Schematic diagrams of the EC/SMC coculture system. ECs and SMCs were seeded on the upper and lower sides of a membrane, respectively. f , g Western blot showing the expression of Notch3, MMP-2, and CNN1 in IL-1b-induced SMCs cocultured with ECs (one-way ANOVA, mean ± S.D.; n = 3). h , i Representative immunofluorescence images of Notch3 expression in the aortic wall of BAPN-induced AAV EC-OE GAD1 mice and vehicle-treated mice ( t test, mean ± S.D.; n = 8, 2 visual fields per sample). Scale bar = 50 μm

Article Snippet: The GABA B receptor antagonist CGP52432 (MCE, USA; catalog: HY-103531; intravenous injection once daily, 10 mg/kg/dose) was administered.

Techniques: Derivative Assay, Western Blot, Expressing, Membrane, Immunofluorescence

Journal: Signal Transduction and Targeted Therapy

Article Title: Endothelial GABA protects against aortic dissection by inhibiting endothelial and mitochondrial dysfunction and maintaining vascular homeostasis

doi: 10.1038/s41392-026-02619-2

Figure Lengend Snippet: Rewiring GABA metabolism reverses vascular homeostasis disorders. a Representative morphology of aortas from the BAPN, GABA 2-week, and GABA + CGP52432 2-week groups. Scale bar = 2 mm. b Incidence of TAD in the BAPN, GABA 2-week, and GABA + CGP52432 2-week groups ( n = 16). c Probability of survival in the BAPN, GABA 2-week, and GABA + CGP52432 2-week groups (log-rank (Mantel‒Cox) test; n = 16). d , e Permeation of Evans blue dye into the thoracic aortas of the BAPN, GABA 2-week, and GABA + CGP52432 2-week groups (one-way ANOVA, mean ± S.D.; n = 3). f , g Representative EVG staining and quantification of elastin degradation in the BAPN, GABA 2-week, and GABA + CGP52432 2-week groups (one-way ANOVA, mean ± S.D.; n = 16). Scale bar = 20 μm. ( h – i ) Representative en face staining of ICAM-1 and statistical data for the aortic wall (one-way ANOVA, mean ± S.D.; n = 6; 2 visual fields per sample). Scale bar = 10 μm. j , k Representative en face staining of c-FOS and statistical data for the aortic wall from differently treated mice ( n = 6, 2 visual fields per sample). Scale bar = 10 μm. l Representative immunofluorescence staining of infiltrating macrophages (F4/80) in the aortic wall of mice subjected to different treatments. Scale bar = 50 μm. m Representative immunofluorescence images of Notch3 expression in the aortic wall of mice subjected to different treatments. Scale bar = 50 μm

Article Snippet: The GABA B receptor antagonist CGP52432 (MCE, USA; catalog: HY-103531; intravenous injection once daily, 10 mg/kg/dose) was administered.

Techniques: Staining, Immunofluorescence, Expressing

Journal: bioRxiv

Article Title: Reduced GABA B receptor activation and post activation depression of proprioceptive afferents after spinal cord injury

doi: 10.64898/2026.01.21.700955

Figure Lengend Snippet: A) Schematic of dorsal root (DR) and ventral root (VR) recordings in response to low-intensity stimulation of Ia afferents in adjacent DR (pink) and optogenetic activation of dorsal (light blue) and ventral (dark blue) projecting GAD2 neurons by blue light in GAD2//ChR2 mice. Dorsal GAD2 neurons innervate GABA A receptors (purple) near Ia nodes to evoke PAD and ventral GAD2 neurons innervate GABA B receptors (green) at Ia terminal to produce presynaptic inhibition, and GABA A receptors on motoneuron to produce an IPSP. Excitatory interneurons between Ia afferent and GAD2 neurons are coloured in lavender. B) DR response to a focused 10 ms light pulse [447nm laser, 0.7 mW/mm 2 , 1.5x light threshold (LT) to evoke PAD or motoneuron responses] applied to dorsal and ventral location of the whole sacral spinal cord (“s” indicates PAD-evoked spike). C) Top: DR response to the same ventral light pulse alone. Middle: DR-evoked EPSP without (pink) and with (blue) prior ventral light pulse, Bottom: DR-evoked EPSP without (blue) and with (green) CGP55845. D) Change in EPSP from prior ventral light pulse without and with CGP55845 (CGP) and in GAD2- mice. E-F) Amplitude of IPSP (E) and PAD (H) from ventral or dorsal light with and without gabazine. G) Dorsal (top) and ventral (bottom) root responses with (blue) and without (pink) PAD evoked from light pulse to dorsal spinal cord with DR-evoked EPSPs triggered during (left) and after (right) PAD. H) Change in EPSP when evoked during and after dorsal light PAD, and during PAD with and without CGP55845 and gabazine (Gbz) (447 nm laser, 1.1xLT). I) Same as in G but with stronger dorsal light pulse to produce PAD-evoked spikes in afferents (green) compared to no-spiking PAD (light blue, 1.2xLT). J) Difference in change in EPSP with PAD-evoked spikes from dorsal light pulse in control and SCI mice and in response to ventral light pulse. In D-J, * indicates p < 0.05 for paired and unpaired comparisons to the control variable; in H-J, + indicates p < 0.001 when the variable is compared to a 0% change or difference (see Supplemental Table 2A for mean (SD) values in D to J and results of statistical comparisons used).

Article Snippet: CGP55845 (abbreviated CGP in figures), a GABA B receptor antagonist (0.3 μM), gabazine, a GABA A receptor antagonist (50 μM) and baclofen, a GABA B receptor agonist (1 μM) (all from Tocris), were added to the nACSF to examine their effects on post-activation depression and Ia hyperpolarization.

Techniques: Activation Assay, Inhibition, Control

Journal: bioRxiv

Article Title: Reduced GABA B receptor activation and post activation depression of proprioceptive afferents after spinal cord injury

doi: 10.64898/2026.01.21.700955

Figure Lengend Snippet: A) Schematic of dorsal root (DR) stimulation and ventral root (VR) recordings to produce post-activation depression of Ia-EPSPs. B) Evoked EPSPs from repetitive DR stimulation every 60ms in GAD2//Arch3 mice without (pink trace) and with (green trace) application of light to silence GAD2 neurons (532nm laser, 5 mW/mm 2 ). Amplitude of 4 th EPSP (M4) is compared to first EPSP (M1). C) Percent change of 4 th EPSP compared to 1 st EPSP in GAD2//Arch3 mice (n = 8 VR recordings from 3 mice) without (white) and with (green) silencing of GAD2 neurons with light. Percentage change of EPSPs in wild type mice (n = 8 VR recordings in 3 mice) without (white) and with (green) GABA B receptor blockade with CGP55845. D-E) Repetitive stimulation of Ia-EPSP from dorsal root stimulation alone (pink traces) and when combined with light pulses to ventral spinal cord (blue traces; 447nm laser, 0.7 mW/mm 2 , 1.5xLT)) in GAD2//ChR2 mice without (D) and during (E) GABA B receptor blockade using CGP55845. F) Repetitive light stimulation of ventral root without (top) and with (bottom) CGP55845 before evoking a test EPSP with DR stimulation. Light blue trace (top) shows small EPSP from PAD-evoked spike. G) Change in Ia-EPSP size in response to repetitive dorsal root, ventral light or combined stimulation with and without CGP845 to indicate GABA B receptor effect on post-activation depression. H) Baseline membrane potential of motoneuron in response to repetitive dorsal root stimulation (pink) or ventral light stimulation in GAD2//ChR2 mice without, and in presence of, CGP55845 and gabazine (GBZ). In C and G, * indicates p < 0.05 for paired Student t-tests and in H, + indicates p < 0.05 from a 0 mV change. Supplemental Table 2B contains mean (SD) values in C, G and H and results of statistical comparisons used.

Article Snippet: CGP55845 (abbreviated CGP in figures), a GABA B receptor antagonist (0.3 μM), gabazine, a GABA A receptor antagonist (50 μM) and baclofen, a GABA B receptor agonist (1 μM) (all from Tocris), were added to the nACSF to examine their effects on post-activation depression and Ia hyperpolarization.

Techniques: Activation Assay, Membrane

Journal: bioRxiv

Article Title: Reduced GABA B receptor activation and post activation depression of proprioceptive afferents after spinal cord injury

doi: 10.64898/2026.01.21.700955

Figure Lengend Snippet: A) Schematic of immunolabelling of Ia afferents and GAD2+ interneuron terminal and associated GABA B receptors and VGLUT1+ afferent terminals. B) Left: Mean intensity of GABA B receptors on the Ia terminal of SCI mice as a % of the intensity in intact mice, with pairs of injured and control spinal cord sections placed on the same slide for labelling. Right: Mean intensity of GABA B receptors on the motoneuron of SCI mice as a % of the intensity on the motoneurons of control mice. C) Mean intensity of GABA B receptors on the Ia terminal as a % of the intensity on the motoneuron for SCI and control mice. D) Mean number of terminals with GABA B receptors as a % of all identified Ia terminals. E-F) Transverse section of spinal cords from intact ( E ) and chronic SCI ( F ) mice whose afferents were labeled with tdTOM (red; AAV9-tdTom), GABA B receptors in green and GAD2 interneurons in blue in GAD2//ChR2-EYFP mice (top row). Lower left panels showing enlarged images of afferents (2nd row), GABA B receptors (3rd row), GAD2 neurons (4th row) and merged picture from all three (5 th row). Right panels: expanded view of Ia afferent terminal for data on left with additional labelling of Ia terminal with VGLUT1 in 4th and 5 th row. GABA B receptors computed to be in the volume of the terminal are rendered yellow. N = 5 mice per group. * p < 0.05 for unpaired Student’s t-tests. Mean (SD) and statistical results in Supplemental Table 2C.

Article Snippet: CGP55845 (abbreviated CGP in figures), a GABA B receptor antagonist (0.3 μM), gabazine, a GABA A receptor antagonist (50 μM) and baclofen, a GABA B receptor agonist (1 μM) (all from Tocris), were added to the nACSF to examine their effects on post-activation depression and Ia hyperpolarization.

Techniques: Control, Labeling

Journal: bioRxiv

Article Title: Reduced GABA B receptor activation and post activation depression of proprioceptive afferents after spinal cord injury

doi: 10.64898/2026.01.21.700955

Figure Lengend Snippet: A) Schematic of dorsal root (DR) and ventral root (VR) recordings in response to low-intensity stimulation of Ia afferents in adjacent DR (pink) and optogenetic activation of dorsal (light blue) and ventral (dark blue) projecting GAD2 neurons by blue light in GAD2//ChR2 mice. Dorsal GAD2 neurons innervate GABA A receptors (purple) near Ia nodes to evoke PAD and ventral GAD2 neurons innervate GABA B receptors (green) at Ia terminal to produce presynaptic inhibition, and GABA A receptors on motoneuron to produce an IPSP. Excitatory interneurons between Ia afferent and GAD2 neurons are coloured in lavender. B) DR response to a focused 10 ms light pulse [447nm laser, 0.7 mW/mm 2 , 1.5x light threshold (LT) to evoke PAD or motoneuron responses] applied to dorsal and ventral location of the whole sacral spinal cord (“s” indicates PAD-evoked spike). C) Top: DR response to the same ventral light pulse alone. Middle: DR-evoked EPSP without (pink) and with (blue) prior ventral light pulse, Bottom: DR-evoked EPSP without (blue) and with (green) CGP55845. D) Change in EPSP from prior ventral light pulse without and with CGP55845 (CGP) and in GAD2- mice. E-F) Amplitude of IPSP (E) and PAD (H) from ventral or dorsal light with and without gabazine. G) Dorsal (top) and ventral (bottom) root responses with (blue) and without (pink) PAD evoked from light pulse to dorsal spinal cord with DR-evoked EPSPs triggered during (left) and after (right) PAD. H) Change in EPSP when evoked during and after dorsal light PAD, and during PAD with and without CGP55845 and gabazine (Gbz) (447 nm laser, 1.1xLT). I) Same as in G but with stronger dorsal light pulse to produce PAD-evoked spikes in afferents (green) compared to no-spiking PAD (light blue, 1.2xLT). J) Difference in change in EPSP with PAD-evoked spikes from dorsal light pulse in control and SCI mice and in response to ventral light pulse. In D-J, * indicates p < 0.05 for paired and unpaired comparisons to the control variable; in H-J, + indicates p < 0.001 when the variable is compared to a 0% change or difference (see Supplemental Table 2A for mean (SD) values in D to J and results of statistical comparisons used).

Article Snippet: CGP55845 (abbreviated CGP in figures), a GABA B receptor antagonist (0.3 μM), gabazine, a GABA A receptor antagonist (50 μM) and baclofen, a GABA B receptor agonist (1 μM) (all from Tocris), were added to the nACSF to examine their effects on post-activation depression and Ia hyperpolarization.

Techniques: Activation Assay, Inhibition, Control

Journal: bioRxiv

Article Title: Reduced GABA B receptor activation and post activation depression of proprioceptive afferents after spinal cord injury

doi: 10.64898/2026.01.21.700955

Figure Lengend Snippet: A) Schematic of dorsal root (DR) stimulation and ventral root (VR) recordings to produce post-activation depression of Ia-EPSPs. B) Evoked EPSPs from repetitive DR stimulation every 60ms in GAD2//Arch3 mice without (pink trace) and with (green trace) application of light to silence GAD2 neurons (532nm laser, 5 mW/mm 2 ). Amplitude of 4 th EPSP (M4) is compared to first EPSP (M1). C) Percent change of 4 th EPSP compared to 1 st EPSP in GAD2//Arch3 mice (n = 8 VR recordings from 3 mice) without (white) and with (green) silencing of GAD2 neurons with light. Percentage change of EPSPs in wild type mice (n = 8 VR recordings in 3 mice) without (white) and with (green) GABA B receptor blockade with CGP55845. D-E) Repetitive stimulation of Ia-EPSP from dorsal root stimulation alone (pink traces) and when combined with light pulses to ventral spinal cord (blue traces; 447nm laser, 0.7 mW/mm 2 , 1.5xLT)) in GAD2//ChR2 mice without (D) and during (E) GABA B receptor blockade using CGP55845. F) Repetitive light stimulation of ventral root without (top) and with (bottom) CGP55845 before evoking a test EPSP with DR stimulation. Light blue trace (top) shows small EPSP from PAD-evoked spike. G) Change in Ia-EPSP size in response to repetitive dorsal root, ventral light or combined stimulation with and without CGP845 to indicate GABA B receptor effect on post-activation depression. H) Baseline membrane potential of motoneuron in response to repetitive dorsal root stimulation (pink) or ventral light stimulation in GAD2//ChR2 mice without, and in presence of, CGP55845 and gabazine (GBZ). In C and G, * indicates p < 0.05 for paired Student t-tests and in H, + indicates p < 0.05 from a 0 mV change. Supplemental Table 2B contains mean (SD) values in C, G and H and results of statistical comparisons used.

Article Snippet: CGP55845 (abbreviated CGP in figures), a GABA B receptor antagonist (0.3 μM), gabazine, a GABA A receptor antagonist (50 μM) and baclofen, a GABA B receptor agonist (1 μM) (all from Tocris), were added to the nACSF to examine their effects on post-activation depression and Ia hyperpolarization.

Techniques: Activation Assay, Membrane

Journal: bioRxiv

Article Title: Reduced GABA B receptor activation and post activation depression of proprioceptive afferents after spinal cord injury

doi: 10.64898/2026.01.21.700955

Figure Lengend Snippet: A) Schematic of immunolabelling of Ia afferents and GAD2+ interneuron terminal and associated GABA B receptors and VGLUT1+ afferent terminals. B) Left: Mean intensity of GABA B receptors on the Ia terminal of SCI mice as a % of the intensity in intact mice, with pairs of injured and control spinal cord sections placed on the same slide for labelling. Right: Mean intensity of GABA B receptors on the motoneuron of SCI mice as a % of the intensity on the motoneurons of control mice. C) Mean intensity of GABA B receptors on the Ia terminal as a % of the intensity on the motoneuron for SCI and control mice. D) Mean number of terminals with GABA B receptors as a % of all identified Ia terminals. E-F) Transverse section of spinal cords from intact ( E ) and chronic SCI ( F ) mice whose afferents were labeled with tdTOM (red; AAV9-tdTom), GABA B receptors in green and GAD2 interneurons in blue in GAD2//ChR2-EYFP mice (top row). Lower left panels showing enlarged images of afferents (2nd row), GABA B receptors (3rd row), GAD2 neurons (4th row) and merged picture from all three (5 th row). Right panels: expanded view of Ia afferent terminal for data on left with additional labelling of Ia terminal with VGLUT1 in 4th and 5 th row. GABA B receptors computed to be in the volume of the terminal are rendered yellow. N = 5 mice per group. * p < 0.05 for unpaired Student’s t-tests. Mean (SD) and statistical results in Supplemental Table 2C.

Article Snippet: CGP55845 (abbreviated CGP in figures), a GABA B receptor antagonist (0.3 μM), gabazine, a GABA A receptor antagonist (50 μM) and baclofen, a GABA B receptor agonist (1 μM) (all from Tocris), were added to the nACSF to examine their effects on post-activation depression and Ia hyperpolarization.

Techniques: Control, Labeling