AA92593
目录号 : GC61951
An OPN4 receptor antagonist
Cas No.:457961-34-1
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
AA92593 is an opsin 4 (OPN4) receptor antagonist (Ki = 16 nM).1 It inhibits light-induced calcium transients in CHO cells expressing human OPN4 (IC50 = 665 nM). AA92593 (10 ?M) reverses light-induced calcium influx in rat intrinsically photosensitive retinal ganglion cells (ipRGCs). In vivo, AA92593 (30 mg/kg) reduces light-induced pupil constriction in mice.
1.Jones, K.A., Hatori, M., Mure, L.S., et al.Small-molecule antagonists of melanopsin-mediated phototransductionNat. Chem. Biol.9(10)630-635(2013)
| Cas No. | 457961-34-1 | SDF | |
| Canonical SMILES | O=S(N1CCCCC1)(C2=CC=C(OC)C(C)=C2)=O | ||
| 分子式 | C13H19NO3S | 分子量 | 269.36 |
| 溶解度 | DMSO : 250 mg/mL (928.13 mM) | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.7125 mL | 18.5625 mL | 37.125 mL |
| 5 mM | 0.7425 mL | 3.7125 mL | 7.425 mL |
| 10 mM | 0.3713 mL | 1.8563 mL | 3.7125 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Regulation of Retinal Melanopsin on Lens-induced Myopia in Guinea Pigs
Optom Vis Sci 2020 Jul;97(7):489-495.PMID:32697555DOI:10.1097/OPX.0000000000001529.
Significance: Investigation of the mechanism and the role of melanopsin in lens-induced myopia is necessary to find out potential targets in the prevention of myopia development. Purpose: We aimed to study the effect and mechanism of retinal melanopsin on lens-induced myopia in guinea pigs, as well as the interactions between melanopsin and other myopic regulation neurotransmitters such as dopamine and melatonin, and to explore the possible role of melanopsin in the prevention of myopia development. Methods: Twenty-day-old tricolor guinea pigs were randomly divided into four groups: control group, defocus group, defocus + AA92593 group, and defocus + dimethyl sulfoxide (DMSO) group. The defocus eyes wore -6.00 D lens. In the defocus + AA92593 group, the vitreous cavities were injected with melanopsin antagonist AA92593. In the defocus + DMSO group, the vitreous cavities were injected with 5% DMSO as the administration control. The expression of retinal melanopsin protein was measured with immunofluorescence staining and Western blot. The content of dopamine and melatonin in the retina was determined by the high-performance liquid chromatography electrochemical method. Results: Compared with the defocus group, intravitreal injection of AA92593 resulted in increased axial length of the defocus eyes (defocus, 8.05 ± 0.09 mm; defocus + AA92593, 8.15 ± 0.11 mm; P = .008), lower refractive degree (defocus, -1.98 ± 0.82 D; defocus + AA92593, -2.59 ± 0.97 D; P = .05), decreased relative expression of retinal melanopsin protein (defocus, 0.67 ± 0.11; defocus + AA92593, 0.20 ± 0.06; P < .0001), and increased melatonin content in the defocus eyes (defocus, 0.38 ± 0.09 ng/mg; defocus + AA92593, 0.55 ± 0.13 ng/mg; P = .01), but it had no obvious effect on dopamine content (defocus, 0.64 ± 0.18 ng/mg; defocus + AA9259, 0.61 ± 0.17 ng/mg; P > .99). The melatonin content of retina in the defocus + AA92593 group was correlated with refractive error (Pearson correlation coefficient = -0.68, P = .006) and eye axis length (Pearson correlation coefficient = 0.74, P = .02). Conclusions: Retinal melanopsin has inhibitory effect on lens-induced myopia development in guinea pigs, and such effect may be related to retinal melatonin.
Light-induced ATP release from the lens
Purinergic Signal 2018 Dec;14(4):499-504.PMID:30238191DOI:10.1007/s11302-018-9626-3.
The recent discovery of the photoreceptor melanopsin in lens epithelial cells has opened the possibility of modulating this protein by light stimulation. Experiments carried out on New Zealand white rabbits have demonstrated that the release of ATP from the lens to the aqueous humor can be reduced either when a yellow filter or a melanopsin antagonist is used. Compared to control (1.10 ± 0.15 μM ATP), the application of a yellow filter (λ465-480) reduced ATP in the aqueous humor 70%, while the melanopsin antagonist AA92593 reduced the presence of ATP 63% (n = 5), an effect which was also obtained with the PLC inhibitor U73122. These results indicate that when melanopsin is blocked either by the lack of light, a filter, or an antagonist, the extracellular presence of ATP is significantly reduced. This discovery may be relevant, on the one hand, because many ocular physiological processes are controlled by ATP and, on the other hand, because it is possible to stimulate ATP release with just light and without using any added substance.
Melanopsin, a Canonical Light Receptor, Mediates Thermal Activation of Clock Genes
Sci Rep 2017 Oct 25;7(1):13977.PMID:29070825DOI:10.1038/s41598-017-13939-3.
Melanopsin (OPN4) is a photo-pigment found in a small subset of intrinsically photosensitive ganglion cells (ipRGCs) of the mammalian retina. These cells play a role in synchronizing the central circadian pacemaker to the astronomical day by conveying information about ambient light to the hypothalamic suprachiasmatic nucleus, the site of the master clock. We evaluated the effect of a heat stimulus (39.5 °C) on clock gene (Per1 and Bmal1) expression in cultured murine Melan-a melanocytes synchronized by medium changes, and in B16-F10 melanoma cells, in the presence of the selective OPN4 antagonist AA92593, or after OPN4 knockdown by small interfering RNA (siRNA). In addition, we evaluated the effects of heat shock on the localization of melanopsin by immunocytochemistry. In both cell lines melanopsin was found in a region capping the nucleus and heat shock did not affect its location. The heat-induced increase of Per1 expression was inhibited when melanopsin was pharmacologically blocked by AA92593 as well as when its protein expression was suppressed by siRNA in both Melan-a and B16-F10 cells. These data strongly suggest that melanopsin is required for thermo-reception, acting as a thermo-opsin that ultimately feeds the local circadian clock in mouse melanocytes and melanoma cells.
Pharmacological induction of skin pigmentation unveils the neuroendocrine circuit regulated by light
Pigment Cell Melanoma Res 2016 Mar;29(2):186-98.PMID:26582755DOI:10.1111/pcmr.12442.
Light-regulated skin colour change is an important physiological process in invertebrates and lower vertebrates, and includes daily circadian variation and camouflage (i.e. background adaptation). The photoactivation of melanopsin-expressing retinal ganglion cells (mRGCs) in the eye initiates an uncharacterized neuroendocrine circuit that regulates melanin dispersion/aggregation through the secretion of alpha-melanocyte-stimulating hormone (α-MSH). We developed experimental models of normal or enucleated Xenopus embryos, as well as in situ cultures of skin of isolated dorsal head and tails, to analyse pharmacological induction of skin pigmentation and α-MSH synthesis. Both processes are triggered by a melanopsin inhibitor, AA92593, as well as chloride channel modulators. The AA9253 effect is eye-dependent, while functional data in vivo point to GABAA receptors expressed on pituitary melanotrope cells as the chloride channel blocker target. Based on the pharmacological data, we suggest a neuroendocrine circuit linking mRGCs with α-MSH secretion, which is used normally during background adaptation.
Yellow Filter Effect on Melatonin Secretion in the Eye: Role in IOP Regulation
Curr Eye Res 2019 Jun;44(6):614-618.PMID:30640554DOI:10.1080/02713683.2019.1570276.
Purpose: Melatonin is a neurohormone mainly synthesized in the pineal gland; however, it is also present in the aqueous humor. One of melatonins' functions in the eye is the regulation of intraocular pressure (IOP). Melatonin is known to be sensitive to light. Recently, the photopigment which controls melatonin synthesis, melanopsin, was found in the crystalline lens. Therefore, light conditions are an interesting possible way of regulating melatonin levels in the aqueous humor. The current study used yellow filters, since melanopsin is activated by short wavelength (blue light). Methods: New Zealand white rabbits were used, divided in two groups, one under controlled 12 h light/dark cycles, while the rest had their cages encased with a yellow filter (λ 465-480). IOP measurements were taken every week at the same time before they were anesthetized for aqueous humor extraction. Results: Keeping the rabbits under the yellow filter resulted in a decrease in IOP up to 43.8 ± 7.8% after 3 weeks. This effect was reversed after the topical application of selective and nonselective melatonin receptors antagonists, 4PPDOT and luzindole. Also, blocking melanopsin by its antagonist AA92593 under white light condition decreased IOP. Finally, melatonin levels were found significantly higher in the aqueous humor of rabbits developed under yellow filter compared to controls (37.4 ± 4.2 and 15.3 ± 3.1 ng/ml, respectively). Conclusion: Yellow filters modulate melatonin levels in the aqueous humor due to deactivating melanopsin activity. This effect leads to a decrease in IOP mediated by melatonin receptors.