Picrotin
(Synonyms: 苦亭) 目录号 : GC38219
A natural antagonist of GlyRs
Cas No.:21416-53-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
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Picrotin is a natural picrotoxane that antagonizes glycine receptors (GlyRs; IC50s = 57 and 117 ?M for α1 and α2 homodimeric GlyRs, respectively).1,2 It also inhibits α3 homodimeric GlyRs.3 Picrotin is inactive in inhibiting γ-aminobutyric acid (GABA) type A and type C receptors. Picrotin occurs in the natural plant-derived poison picrotoxin , equimolar with picrotoxinin.
1.Lynch, J.W., Rajendra, S., Barry, P.H., et al.Mutations affecting the glycine receptor agonist transduction mechanism convert the competitive antagonist, picrotoxin, into an allosteric potentiatorJ. Biol. Chem.270(23)13799-13806(1995) 2.Yang, Z., Cromer, B.A., Harvey, R.J., et al.A proposed structural basis for picrotoxinin and picrotin binding in the glycine receptor poreJ. Neurochem.103(2)580-589(2007)
| Cas No. | 21416-53-5 | SDF | |
| 别名 | 苦亭 | ||
| Canonical SMILES | C[C@]([C@@](C1)([C@]2([H])[C@@](C(O)(C)C)([H])[C@@]3([H])OC2=O)O)([C@]3([H])OC4=O)[C@@]54[C@@H]1O5 | ||
| 分子式 | C15H18O7 | 分子量 | 310.3 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.2227 mL | 16.1134 mL | 32.2269 mL |
| 5 mM | 0.6445 mL | 3.2227 mL | 6.4454 mL |
| 10 mM | 0.3223 mL | 1.6113 mL | 3.2227 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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Mechanisms for picrotoxinin and Picrotin blocks of alpha2 homomeric glycine receptors
J Biol Chem 2007 Jun 1;282(22):16016-35.PMID:17405877DOI:10.1074/jbc.M701502200.
Contrary to its effect on the gamma-aminobutyric acid type A and C receptors, picrotoxin antagonism of the alpha1 homomeric glycine receptors (GlyRs) has been shown to be non-use-dependent and nonselective between the picrotoxin components picrotoxinin and Picrotin. Picrotoxin antagonism of the embryonic alpha2 homomeric GlyR is known to be use-dependent and reflects a channel-blocking mechanism, but the selectivity of picrotoxin antagonism of the embryonic alpha2 homomeric GlyRs between picrotoxinin and Picrotin is unknown. Hence, we used the patch clamp recording technique in the outside-out configuration to investigate, at the single channel level, the mechanism of picrotin- and picrotoxinin-induced inhibition of currents, which were evoked by the activation of alpha2 homomeric GlyRs stably transfected into Chinese hamster ovary cells. Although both picrotoxinin and Picrotin inhibited glycine-evoked outside-out currents, Picrotin had a 30 times higher IC50 than picrotoxinin. Picrotin-evoked inhibition displayed voltage dependence, whereas picrotoxinin did not. Picrotoxinin and Picrotin decreased the mean open time of the channel in a concentration-dependent manner, indicating that these picrotoxin components can bind to the receptor in its open state. When Picrotin and glycine were co-applied, a large rebound current was observed at the end of the application. This rebound current was considerably smaller when picrotoxinin and glycine were co-applied. Both Picrotin and picrotoxinin were unable to bind to the unbound conformation of the receptor, but both could be trapped at their binding site when the channel closed during glycine dissociation. Our data indicate that picrotoxinin and Picrotin are not equivalent in blocking alpha2 homomeric GlyR.
Gating effects on Picrotin block of glycine receptors
Neuroreport 2012 Dec 5;23(17):1017-20.PMID:23079787DOI:10.1097/WNR.0b013e32835a8629.
Picrotoxin is a pore blocker that can differentiate ligand-gated inhibitory chloride channels. Even within one receptor type, such as the glycine receptor, picrotoxin block differs between subunits. The effect of subunit gating properties on block of the inhibitory glycine receptor (GlyR) was explored using heteromeric α subunit expression in voltage-clamped HEK293 cells. The α2 GlyR is more sensitive to Picrotin block than the α1 GlyR, and this difference was used to explore whether mutations that interfered with gating of the α2 subunit would also interfere with Picrotin block. Two mutations were used: one that decreased the glycine sensitivity of α2 by almost two log units and the other that was unresponsive to glycine. In both cases, the sensitivity to Picrotin was essentially unaltered. The results indicated that α2 subunits can determine the Picrotin sensitivity of α1α2-heteromeric receptors and that direct gating of the α2 subunit is not required for this Picrotin inhibition.
A proposed structural basis for picrotoxinin and Picrotin binding in the glycine receptor pore
J Neurochem 2007 Oct;103(2):580-9.PMID:17714449DOI:10.1111/j.1471-4159.2007.04850.x.
Picrotoxin, an antagonist of structurally-rated GABA(A) receptors (GABA(A)Rs) and glycine receptors (GlyRs), is an equimolar mixture of picrotoxinin (PTXININ) and Picrotin (PTN). These compounds share a common structure except that PTN contains a slightly larger dimethylmethanol in place of the PTXININ isopropenyl group. Although the homomeric alpha1 GlyR is equally sensitive to both compounds, we show here that homomeric alpha2 and alpha3 GlyRs, like most GABA(A)Rs, are selectively inhibited by PTXININ. As conservative mutations to pore-lining 6' threonines equally affect the sensitivity of the alpha1 GlyR to both compounds, we conclude that PTXININ and PTN bind to 6' threonines by hydrogen bonding with exocyclic oxygens common to both molecules. In contrast, substitution of the 2' pore-lining glycine by serine selectively reduces PTN sensitivity, whereas the introduction of 2' alanines selectively increases PTXININ sensitivity. These results define the orientation of PTXININ and PTN binding in the alpha1 GlyR pore and allow us to conclude that the relatively reduced sensitivity of PTN at GABA(A)Rs and alpha2 and alpha3 GlyRs is due predominantly to its larger size and reduced ability to form hydrophobic interactions with 2' alanines.
Glycine receptor subunit composition alters the action of GABA antagonists
Vis Neurosci 2007 Jul-Aug;24(4):513-21.PMID:17659095DOI:10.1017/S0952523807070368.
GABA receptor antagonists produce an unexpectedly significant inhibition of native glycine receptors in retina and in alpha1 or alpha2 homomeric glycine receptors (GlyRs) expressed in HEK 293 cells. In this study we evaluate this phenomenon in heteromeric glycine receptors, formed by mixing alpha1, alpha2, and beta subunits. Picrotoxinin, Picrotin, SR95531, and bicuculline are all more effective antagonists at GlyRs containing alpha2 subunits than alpha1 subunits. Inclusion of beta subunits reduces the inhibitory potency of picrotoxinin and Picrotin but increases the potency of SR95531 and bicuculline. As a result of these two factors, bicuculline is particularly poor at discriminating GABA and glycine receptors. Picrotin, which has been reported to be inactive at GABA receptors, blocks glycine currents in retina and in HEK293 cells, suggesting its utility as a selective glycine antagonist. However, Picrotin is a more potent inhibitor of GABA than glycine in retinal neurons. We also tested if GABA and glycine receptor subunits can combine to form functional receptors. If GABAAR gamma2S subunits are co-expressed with GlyR alpha subunits, the mixed receptor is glycine-sensitive and GABA-insensitive. But the mixed receptor exhibits a non-competitive picrotoxinin inhibition that is not observed in the homomeric GlyRs. This suggests that glycine and GABA subunits can co-assemble to form functional glycine receptors.
Picrotoxin as a potent inducer of rat hepatic cytochrome P450, CYP2B1 and CYP2B2
Biochem Pharmacol 1993 May 5;45(9):1783-9.PMID:8494537DOI:10.1016/0006-2952(93)90434-x.
The induction by the central stimulant picrotoxin of hepatic drug-metabolizing enzymes was studied in rats. The hepatic content of P450 and the activity of benzphetamine N-demethylation increased gradually after administration of picrotoxin dissolved in drinking water (2 mg/mL), to three-times higher levels than the initial values at the third day of treatment. The increase in benzphetamine N-demethylase activity by picrotoxin was somewhat higher than the increase produced by phenobarbital. Supporting these results, immunoblot analysis showed that CYP2B1 and 2B2 proteins in the liver microsomes were increased by picrotoxin Picrotoxinin and Picrotin, which are components of the picrotoxin molecule, had the same ability to induce the hepatic activity of benzphetamine N-demethylation. The liver microsomal activities of testosterone 16 alpha- and 16 beta-hydroxylation were enhanced significantly after treatment with picrotoxinin and Picrotin. However, benzo[a]pyrene 3-hydroxylation, aniline 4-hydroxylation, and testosterone hydroxylations at the 2 alpha- and 7 alpha-positions were not increased by picrotoxinin and Picrotin treatment. In addition to monooxygenase, significant induction of glutathione S-transferase activity for 1-chloro-2,4-dinitrobenzene and UDP-glucuronyltransferase activity for 4-hydroxybiphenyl and 4-nitrophenol was also observed by pretreatment of picrotoxin. These results clearly indicate that picrotoxin is an inducer of phenobarbital-inducible liver enzymes.