Picrotoxin (Cocculin) is a plant alkaloid that is a non-competitive antagonist of GABAA receptors and can block the chloride channel of GABAA receptors[1]. Picrotoxin does not act on the GABA recognition site, but may act on ion channels and can act as a central nervous system stimulant, causing excessive stimulation and convulsive reactions [2]. Picrotoxin is a non-competitive antagonist of glycine receptors [3].
In vitro, Picrotoxin (25-1000µM) treated SCN cells, concentration-dependently accelerated the circadian rhythm of cell discharge activity, and Picrotoxin (100µM) selectively advanced the accumulation of PER 2 protein by approximately 3.7 h without affecting PER 2 stability[4]. Picrotoxin (100µM) treated HEK293 cells, significantly inhibiting the expression of 5-HT3A receptors in the cells. Picrotoxin (10-300µM) inhibits 5-HT gated current in cells in a concentration-dependent manner, with an IC50 value of approximately 30µM[5].
In vivo, Picrotoxin (1mg/kg) treated NG2-CreERTM:EYFP mice via intraperitoneal injection for 5 days significantly increased the number and density of OPC neuron pairs[6]. Picrotoxin (2mg/kg) treated female CD rats by intraperitoneal injection increased the acetylcholine content in the striatum by approximately 70% and the level of homovanillic acid by approximately 30% [7].
References:
[1]Carpenter T S, Lau E Y, Lightstone F C. Identification of a possible secondary picrotoxin-binding site on the GABAA receptor[J]. Chemical research in toxicology, 2013, 26(10): 1444-1454.
[2]Olsen R W. Picrotoxin-like channel blockers of GABAA receptors[J]. Proceedings of the National Academy of Sciences, 2006, 103(16): 6081-6082.
[3]Qian H, Pan Y, Zhu Y, et al. Picrotoxin accelerates relaxation of GABAC receptors[J]. Molecular pharmacology, 2005, 67(2): 470-479.
[4]Freeman Jr G M, Nakajima M, Ueda H R, et al. Picrotoxin dramatically speeds the mammalian circadian clock independent of Cys-loop receptors[J]. Journal of neurophysiology, 2013, 110(1): 103-108.
[5]Das P, Bell-Horner C L, Machu T K, et al. The GABAA receptor antagonist picrotoxin inhibits 5-hydroxytryptamine type 3A receptors[J]. Neuropharmacology, 2003, 44(4): 431-438.
[6]Boulanger J J, Messier C. Oligodendrocyte progenitor cells are paired with GABA neurons in the mouse dorsal cortex: Unbiased stereological analysis[J]. Neuroscience, 2017, 362: 127-140.
[7]Ladinsky H, Consolo S, Bianchi S, et al. Increase in striatal acetylcholine by picrotoxin in the rat: evidence for a gabergic-dopaminergic-cholinergic link[J]. Brain Research, 1976, 108(2): 351-361.
Picrotoxin(Cocculin)是一种植物生物碱,是 GABAA受体的非竞争性拮抗剂,可阻断GABAA受体的氯离子通道[1]。Picrotoxin不作用于GABA识别位点,但可能作用于离子通道内,可作为中枢神经系统兴奋剂,会引发过度刺激和惊厥反应[2]。Picrotoxin是甘氨酸受体的非竞争性拮抗剂[3]。
在体外,Picrotoxin(25-1000µM)处理SCN细胞,浓度依赖性地加速了细胞放电活动的昼夜节律,Picrotoxin(100µM)选择性地将PER 2蛋白的积累提前了约3.7 h,而不影响PER 2的稳定性[4]。Picrotoxin(100µM)处理HEK293细胞,显著抑制了细胞表达5-HT3A 受体。Picrotoxin(10-300µM)以浓度依赖性方式抑制细胞中5-HT门控电流,IC50值约为30µM[5]。
在体内,Picrotoxin(1mg/kg)通过腹腔注射处理NG2-CreERTM:EYFP小鼠5天,显著增加了OPC神经元对的数量和密度[6]。Picrotoxin(2mg/kg)通过腹腔注射处理雌性CD大鼠,使纹状体内乙酰胆碱含量增加约70%,高香草酸的水平增加约30%[7]。