FP receptor; prostaglandin F (PGF) receptor; Endogenous Metabolite

当山羊黄体细胞暴露于地诺前列素（前列腺素 F2α；1 μM）一整天时，会发生坏死、自噬和内质网脱垂 [1]。地诺前列素 (1 μM) 在 24 小时内显着升高 GRP78 和 UPR 传感器。

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PGF2α（10（-6）M）和氟前列醇（10（-6M）M）抑制了ET-1诱导的离体BTM（10（-8）M）收缩。这种作用被FP受体拮抗剂阻断。卡巴胆碱诱导的收缩或基线张力不受PGF2alpha或氟前列醇的影响。在培养的TM细胞中，ET-1导致[Ca2+]i短暂增加，而PGF2α会降低[Ca2+]i。在FP受体拮抗剂Al-8810存在的情况下没有发生减少。Western blot分析揭示了FP受体在天然和培养的TM中的表达。 结论：FP受体激动剂通过与ET-1诱导的TM收缩性直接相互作用来发挥作用。这种作用是由FP受体介导的。因此，FP受体激动剂可以通过抑制ET-1依赖性机制来增强通过TM的房水流出，从而降低IOP。[1]

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黄体（CL）是一种短暂的内分泌组织，产生黄体酮以维持哺乳动物的妊娠。此外，CL的回归对于启动动情周期是必要的。广泛的研究表明，前列腺素F2α（PGF2α）诱导反刍动物CL的消退。然而，PGF2α诱导的山羊CL消退中内质网应激和自噬的机制尚不清楚。在这项研究中，收集了发情山羊和怀孕3个月的山羊的卵巢，以检测ER应激相关蛋白GRP78的位置。western blot分析证实了山羊CL在发情周期中黄体期不同阶段与ER应激相关蛋白和自噬相关蛋白表达变化之间的关系。结果表明，在山羊CL的黄体晚期，ER应激和自噬都被激活。为了揭示ER应激和自噬在PGF2α诱导的CL消退过程中的作用，我们分别使用4-苯基丁酸（4-PBA）和氯喹（CQ）抑制ER应激和自体吞噬。通过流式细胞术检测到的凋亡率和蛋白质印迹检测到的ER应激和自噬相关蛋白的表达，我们证明ER应激促进了山羊黄体细胞的凋亡和自噬，并且抑制自噬可以增强凋亡。此外，敲除阻断PERK通路激活的EIF2S1，通过减少PGF2α处理的山羊黄体细胞的自噬来促进凋亡。总之，我们的研究表明，内质网应激通过PERK信号通路促进山羊黄体细胞凋亡以调节CL的回归，并激活自噬以抑制山羊黄体细胞的凋亡[2]。

细胞凋亡分析 [1]
细胞类型： 山羊黄体细胞
测试浓度： 1 μM
孵育时间： 24 hrs（小时）
实验结果：细胞凋亡率显着增加（15.62±3.12%）。自噬检测 [1]
细胞类型： 山羊黄体细胞
测试浓度： 1 μM
孵育时间： 24 hrs（小时）
实验结果：黄体细胞中LC3和LAMP1存在广泛重叠，山羊黄体细胞中形成自噬溶酶体。

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蛋白质印迹分析[1]
细胞类型： 山羊黄体细胞
测试浓度： 1 μM
孵育持续时间：24小时
实验结果：GRP78和UPR传感器的表达，包括裂解的ATF6、磷酸-EIF2S1、EIF2S1、ATF4、磷酸-IRE1、自体吞噬作用相关胞内蛋白LC3-II和促凋亡因子cleaved Caspase3显着增加。

Goat ovaries were collected from sexually mature healthy goats and from goats that were pregnant for 3 months in a local abattoir within 10–20 min of slaughter. The duration of pregnancy was determined by the size and morphological characteristics of the fetus. Fresh ovaries stored on ice were taken back to our laboratory within 30 min for subsequent sampling. The complete CL was exfoliated during the estrous cycle from the non-pregnant goats’ ovaries on ice, and each CL was divided into two equal parts. These CL tissues were frozen in liquid nitrogen and stored at −80°C until RNA and protein extraction. Based on the detection of morphological characteristics and the levels of marker genes’ expression, such as STAR, 3βHSD, LH-R, and CYP19A1, in these goat CLs as previously described (Farin et al., 1986), the stages of the luteal phase of the CLs were categorized into five main groups [i.e., early (1–3 day after ovulation), mid1 (4–7 day after ovulation), mid2 (8–12 day after ovulation), mid3 (13–16 day post-ovulation), and late (17–20 post-ovulation)] (Figures 1B,C). For one independent experiment, we exfoliated goat CLs from at least three ovaries in each luteal stage (n = 3 ovaries per stage). All other ovaries fixed in paraformaldehyde (4%) for immunohistochemistry analysis were collected from three dioestrus goats and three pregnant goats.

Absorption, Distribution and Excretion
Currently studied seminal compounds include prostaglandins (25 mg/ml). /Prostaglandins/ Aside from typically slow and species-dependent isomerization, PGS E and PGS F are fairly stable in the blood, but they are rapidly degraded and inactivated by tissue-binding enzymes; approximately 80-90% or more is destroyed during a single passage through the liver or lungs. /Prostaglandins/ The degree of binding of prostaglandins to plasma proteins appears to have little effect on their metabolic and clearance rates. …Whether prostaglandins are administered in free form or bound to rat plasma albumin, the clearance rate of (3)H remains unchanged. /Prostaglandins/

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Metabolism/Metabolites …Prostaglandin metabolism is rapid… /Prostaglandins/

Interactions
Fenamic acid, phenylbutazone, and aspirin (with weaker effects) can inhibit the contractile response of isolated human bronchial muscle to prostaglandin F2α.

[1]. Endothelin antagonism: effects of FP receptor agonists prostaglandin F2alpha and fluprostenol on trabecular meshwork contractility. Invest Ophthalmol Vis Sci. 2006 Mar;47(3):938-45.

[2]. Prostaglandin F2α Induces Goat Corpus Luteum Regression via Endoplasmic Reticulum Stress and Autophagy. Front Physiol. 2020 Sep 11;11:868.

Prostaglandin F2α is a prostaglandin Fα with the structure prostaglandin-5,13-diene-1-acid, substituted with hydroxyl groups at positions 9, 11, and 15. It is a naturally occurring prostaglandin used for labor induction. It is a metabolite in both humans and mice. It is a prostaglandin Fα and a monocarboxylic acid. It is the conjugate acid of prostaglandin F2α(1-). Dinoprost has been used to treat headaches. Dinoprost has been reported in Homo sapiens, Japanese deer, and other organisms with relevant data. Dinoprost is a synthetic analogue of naturally occurring prostaglandin F2α. Prostaglandin F2α stimulates uterine myometrial activity, relaxes the cervix, inhibits progesterone production, and induces luteal dissolution through direct action on the corpus luteum. (NCI04) Prostaglandin F2α is a naturally occurring prostaglandin that stimulates uterine myometrial activity, relaxes the cervix, inhibits progesterone production, and induces luteal dissolution through direct action on the corpus luteum. Elevated expression of prostaglandin F2α (PGF2) is observed in certain types of cancer. A naturally occurring prostaglandin, it has oxytocin, luteolytic, and abortifacient effects. Due to its vasoconstrictive properties, this compound also has a variety of other biological functions. See also: dinoprost tromethamine (salt form). Mechanism of Action: ...There is no single prostaglandin receptor. ...Multiple responses to prostaglandins have been shown to be calcium-dependent, and alterations in calcium flow have been observed. ...Prostaglandins can both stimulate and inhibit the accumulation of cyclic adenosine monophosphate (cAMP). Prostaglandins: Responses to prostaglandin F2α vary among species, but vasodilation has been observed after injection of PGF2α into the human brachial artery...PGF2α can cause vasoconstriction in the superficial veins of the hand...Parenteral injection of prostaglandin F2α rapidly reduces progesterone secretion and causes corpus luteum degeneration...This effect can interrupt early pregnancy, which depends on corpus luteum rather than placental progesterone. Oxytocin and prostaglandins affect uterine smooth muscle through different mechanisms. The mechanisms of action and effects of these drugs are additive. The potential benefits of combined use are currently being explored. /Prostaglandins/

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Therapeutic Uses
Nonsteroidal abortifacients; oxytocin
…Some doctors prefer to postpone abortion until after 16 weeks of gestation, when the intra-amniotic route can be performed more safely. /Denoprost Tromethamine/
Extra-amniotic route (currently under investigation) requires the placement of an indwelling catheter in the uterus outside the ovary via the vagina. ...Used only for termination of pregnancy between 13 and 15 weeks of gestation... /Denoprost Tromethamine/
Intrauterine administration achieves effective concentrations within the myometrium, requiring the lowest possible dose. Intra-amniotic instillation is performed by inserting a long spinal needle into the amniotic sac via the abdomen. /Denoprost Tromethamine/
For more complete data on the therapeutic uses of prostaglandin F2α (15 in total), please visit the HSDB record page.

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Drug Warnings
Asthmatic patients are particularly sensitive; PGF2α has been shown to cause severe bronchospasm.
Some researchers have noted that prostaglandins may exhibit a narrow dose-response range in producing physiological contractions and causing excessive uterine tone; this potential risk can be avoided by very cautiously increasing the infusion rate gradually. Prostaglandin drugs used for mid-pregnancy abortion…can cause…common but tolerable side effects. However, for very early abortion (menstrual delay of several weeks), success rates have been reported to be low, and the required doses can cause serious side effects. Prostaglandins are contraindicated in acute pelvic inflammatory disease. Caution should be exercised in patients with a history of hypertension, asthma, glaucoma, epilepsy, or cardiovascular disease. For more complete data on drug warnings for prostaglandin F2α (11 in total), please visit the HSDB records page.

C20H34O5

354.4810

354.24

C, 67.77; H, 9.67; O, 22.57

551-11-1

Dinoprost tromethamine salt;38562-01-5;(5R)-Dinoprost;4510-16-1;Dinoprost-d4;34210-11-2;Dinoprost-d9

5280363

White to light brown <25°C powder,>35°C liquid

1.2±0.1 g/cm3

531.0±50.0 °C at 760 mmHg

120°C

289.0±26.6 °C

0.0±3.2 mmHg at 25°C

1.569

2.14

97.99

4

5

12

25

432

5

O([H])[C@@]1([H])C([H])([H])[C@]([H])([C@]([H])(/C(/[H])=C(\[H])/[C@]([H])(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])O[H])[C@@]1([H])C([H])([H])/C(/[H])=C(/[H])\C([H])([H])C([H])([H])C([H])([H])C(=O)O[H])O[H]

PXGPLTODNUVGFL-YNNPMVKQSA-N

InChI=1S/C20H34O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h4,7,12-13,15-19,21-23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,18-,19+/m0/s1

(Z)-7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((S,E)-3-hydroxyoct-1-en-1-yl)cyclopentyl)hept-5-enoic acid

Cerviprost; HSDB 3315; Panacelan; Prostaglandin F2a; Prostaglandin F2alpha; Prostaglandin F2a; PGF2alpha; amoglandin; Enzaprost; Protamodin;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~282.10 mM)
DMSO : ~100 mg/mL (~282.10 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (7.05 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (7.05 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。