(+)-Bicuculline is a light-sensitive competitive antagonist of GABA-A receptor[3]. Bicuculline (25 mM) markedly potentiated Ca2+ transients caused by KCl (25 mM) and by A23187 (4 mM) whereas gabazine (25 mM) had no effect. Bicuculline triggers calcium release when calcium entry is evoked by KCl or A23187 and that this effect is not mediated via GABA(A) receptor blockade[4]. Bicuculline (20-100 micrometers) depressed the GABA-evoked conductance increase in a reversible manner, the double reciprocal transformation of the GABA dose/conductance curves remaining linear. Combinations of bicuculline and picrotoxinin also depressed the GABA response in a manner expected from the combination of two "mixed" non-competitive antagonists. Bicuculline (like picrotoxinin and picrotoxin) behaves as a "mixed" non-competitive rather than a pure non-competitive antagonist of GABA on lobster muscle[5]. Intracerebroventricular administration of 0.3 and 0.5 nmol of bicuculline produces an increase in blood pressure and a slight bradycardia in non-epileptic Wistar rats. The blood pressure response to intracerebroventricular bicuculline is significantly potentiated in epileptic WAG/Rij rats. Additionally, the pressor effect of 0.5 nmol of bicuculline is not attenuated by bilateral electrolytic ablation of the central nucleus of the amygdala in WAG/Rij rats[6].
Bicuculline/(+)-荷包牡丹碱 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mouse small intestinal organoids
1 µM
1-hour pretreatment
Bicuculline pretreatment significantly mitigated 5-FU/irradiation-induced toxicity in organoids, improved ISC growth, and reduced p-P53, γ-H2AX, and Cleaved Caspase 3 protein levels.
J Exp Med. 2022 Dec 5;219(12):e20220541.
HEK293 cells
100 µM
42 seconds
To verify the inhibitory effect of Bicuculline on α1β3γ2L receptors
Nature. 2019 Jan;565(7740):454-459.
DI TNC1 rat astrocytes
100 µM
5 min
To evaluate the effect of GABA A receptor antagonist bicuculline on GABA-induced increase in Cx43 hemichannel activity. Results showed that bicuculline completely prevented the GABA-induced increase in DAPI uptake.
Int J Mol Sci. 2022 Nov 7;23(21):13625.
Rat hippocampal neuron-glial cell cultures
10 µM
To investigate the mechanisms of PDS generation and maintenance, it was found that AMPAR antagonist NBQX completely suppressed bicuculline-induced paroxysmal activity
Int J Mol Sci. 2023 Jul 1;24(13):10991.
Bicuculline/(+)-荷包牡丹碱 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
Hypertension model
PVN microinjection
0.1 nmol
Single injection
To investigate the effect of Ang II on the response to GABA-A receptor antagonism in the PVN. Results showed that Ang II infusion significantly blunted the increase in renal SNA, MAP, and HR induced by BMI.
Hypertension. 2003 Dec;42(6):1124-9
Macaque monkeys
Acute seizure model
Intracerebral injection
0.1-4 μL (0.4-16 μg)
Single injection, observed for 1-2 hours
Bicuculline was used to induce acute seizures in the primary motor cortex of macaque monkeys, resulting in contralateral arm twitching and stiffening, followed by hemi- and whole-body clonic seizures. The study demonstrated the efficacy of Bicuculline in inducing an epilepsy model.
Nat Commun. 2023 Feb 28;14(1):971
Rhesus monkeys (Macaca mulatta)
Inhibition model of cvGPe neurons in monkeys
Local injection
1 μg/μl
Single injection, behavioral tests started 5 minutes after injection
To study the role of the indirect pathway in suppressing saccades to bad objects by blocking GABAergic inputs to cvGPe neurons. Results showed that after injection, monkeys were unable to suppress saccades to bad objects, indicating the critical role of the indirect pathway in rejecting bad choices.
Sci Adv. 2019 Aug 7;5(8):eaaw9297
Rats
Hippocampal slices
In vitro incubation
100 µM
Preincubation for 10 min, followed by GABA incubation for 5 min
To evaluate the effect of bicuculline on GABA-induced increase in Cx43 hemichannel activity in hippocampal slices. Results showed that bicuculline completely blunted the GABA-induced increase in Etd+ uptake.
Int J Mol Sci. 2022 Nov 7;23(21):13625.
Rats
Area Tempestas and amygdala kindling models
Microinjection
100-200 pmol
Single injection
Recorded single unit activity from the nRT prior to, and after infusion of bicuculline into the Area Tempestas, and found that the mean firing rate in the nRT was decreased after infusion.
Epilepsia. 2021 Sep;62(9):2283-2296
Mice
WT C57BL/6J and genetically modified models (ApcMin/+, Gabra1IEC-KO, Gabra1Lgr5-KO)
Intraperitoneal injection
2 mg/kg
Once every 2 days (tumor models) or single dose (chemoradiotherapy protection)
Bicuculline alleviated intestinal structural damage (e.g., villus shortening, reduced TACs/OLFM4+ ISCs) and decreased γ-H2AX/apoptotic markers without compromising tumor chemoradiosensitivity.
J Exp Med. 2022 Dec 5;219(12):e20220541.
Sprague-Dawley rats
Adult male rats
Bilateral pressure injection
200 µM
Single injection, recorded for 20-25 minutes
To investigate the impact of GABAergic disinhibition on respiration, it was found that the rostral pFL region is most critical for the generation of active expiration.
Elife. 2024 Jul 17;13:RP94276
Male Wistar rats
Uninephrectomized anesthetized rats
Injection into the paraventricular nucleus of hypothalamus
4 mM
Single injection
To evaluate the effects of acute increases in blood pressure and renal sympathetic nerve activity on sodium and water excretion. Results showed that Bic injection increased blood pressure and renal sympathetic nerve activity, followed by diuresis and natriuresis, along with increased phosphorylation of NHE3 at serine 552.
Int J Mol Sci. 2022 Dec 26;24(1):349
Mice
Awake and isoflurane-anesthetized mice
Subcortical injection
5 mM
Single injection, lasting 2-3 hours
To investigate the effects of isoflurane anesthesia on neuronal activity and hemodynamic responses. Results showed that isoflurane significantly reduced LFP amplitude but had little effect on calcium signal amplitude and area. Anesthesia also dramatically blunted the amplitude and latency of the hemodynamic response, although not its area of spread.
J Cereb Blood Flow Metab. 2024 Jun;44(6):911-924
Bicuculline/(+)-荷包牡丹碱 动物研究
Animal study
癫痫[7]
动物：BD IX 大鼠，雌性，140-170 g。
给药：1.2 mg/kg，静脉注射，单剂量。
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