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

地诺前列素氨丁三醇盐（前列腺素 F2α 氨丁三醇盐；1 μM；持续 24 小时）可诱导山羊黄体细胞内质网应激、自噬和细胞凋亡[1]。地诺前列素氨丁三醇盐（1 μM；持续 24 小时）显着增加 GRP78 和 UPR 传感器的表达[1]。细胞凋亡分析[1] 细胞系：山羊黄体细胞 浓度：1 μM 孵育时间：24 小时 结果：细胞凋亡率显着增加（15.62±3.12%）。细胞自噬检测[1] 细胞系：山羊黄体细胞 浓度：1 μM 孵育时间：24小时 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。 Western Blot分析[1] 细胞系：山羊黄体细胞 浓度：1 μM 孵育时间：24小时 结果：GRP78和UPR传感器的表达，包括裂解的ATF6、磷酸化-EIF2S1、EIF2S1、ATF4、磷酸化-IRE1、自噬相关细胞内蛋白质LC3-II和促凋亡因子cleaved Caspase3显着增加。

在第二次治疗后，间隔14天使用两次PGF（2α）治疗来提高发情检测率是一种生殖管理工具，继续在大型奶牛场使用。在一项研究中，在具有功能性CL和优势卵泡的奶牛中，与地诺前列素相比，氯前列醇治疗导致外周雌二醇浓度更高。本研究的目的是确定使用PGF（2α）程序进行第一次人工授精（AI）时，氯前列烯醇是否可以提高大型奶牛群中奶牛的妊娠率。哺乳期奶牛（n=4549）被随机分配接受两种治疗，即500μg氯前列醇或25mg地诺前列素，间隔14天，第二种治疗在自愿等待期（57DIM）的第一天进行。在第二次治疗后5天内发现处于发情期的奶牛被授精。在发情检测当天，治疗没有效果，78%的奶牛在治疗后的第3天或第4天受精。与地诺前列素相比，氯前列醇提高了一胎奶牛的发情检测率（P<0.01），分别为42.4%和34.0%。在治疗后第3或4天受精的奶牛中，与地诺前列素相比，氯前列醇提高了受孕率（P=0.05），分别为38.3%和34.4%。当治疗和分娩相结合时，受孕率随着治疗后间隔的增加而增加（P<0.02）（第1或2天、第3或4天和第5天分别为27.0%、36.4%和44.5%）。与地诺前列素相比，氯前列醇提高了总体妊娠率（P=0.02），分别为14.4%和12.2%。总之，与地诺前列素相比，氯前列醇提高了治疗后第3天或第4天受精的第一胎奶牛的生育能力，随后提高了第一胎泌乳奶牛的妊娠率。预计在治疗时有一个年轻的窦状卵泡的奶牛的生育能力似乎更高[3]。

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] 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]。

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.[2]

Absorption, Distribution and Excretion
Slowly absorbed from the amniotic fluid into systemic circulation.

---

Metabolism / Metabolites
Enzymatic dehydrogenation primarily in the maternal lungs and also in the liver.

---

Biological Half-Life
The half-life of dinoprost in amniotic fluid is 3 to 6 hours. The plasma half-life of dinoprost after intravenous administration is reported to be less than 1 minute.

[1]. Invest Ophthalmol Vis Sci. 2006 Mar;47(3):938-45.

[2]. Front Physiol. 2020 Sep 11:11:868.

[3]. Compared to dinoprost tromethamine, cloprostenol sodium increased rates of estrus detection, conception and pregnancy in lactating dairy cows on a large commercial dairy. Theriogenology. 2012 Sep 1;78(4):823-9.

Dinoprost tromethamine is an organic molecular entity.
The tromethamine (THAM) salt of the naturally occurring prostaglandin F2 alpha, dinoprost tromethamine occurs as a white to off-white, very hygroscopic, crystalline powder. Dinoprost tromethamine may also be known as dinoprost trometamol, PGF2 alpha THAM, or prostaglandin F2 alpha tromethamine.
Dinoprost Tromethamine is a synthetic analogue of the naturally occurring prostaglandin F2 alpha. Prostaglandin F2 alpha stimulates myometrial activity, relaxes the cervix, inhibits corpus luteal steroidogenesis, and induces luteolysis by direct action on the corpus luteum. (NCI04)
See also: Dinoprost (has active moiety).

---

Drug Indication
Used for aborting second-trimester pregnancy (between the twelfth to eighteenth week of gestation) and in incomplete abortion or for therapeutic abortion in cases of intrauterine fetal death and congenital abnormalities incompatible with life. Also used at low-doses for medically indicated induction of labor at term. Also injected intra-arterially for use as a vasodilator to assist in angiography.

---

Mechanism of Action
Dinoprost tromethamine appears to act directly on the myometrium, but this has not been completely established. Dinoprost stimulates myometrial contractions (via its interaction with the prostaglandin receptors) in the gravid uterus that are similar to the contractions that occur in the term uterus during labor. These contractions are usually sufficient to cause abortion. Uterine response to prostaglandins increases gradually throughout pregnancy. Dinoprost also facilitates cervical dilatation and softening.

---

Pharmacodynamics
Dinoprost tromethamine is the tromethamine (THAM) salt of the naturally occurring prostaglandin F2_alpha. Prostaglandin F2_alpha has several pharmacologic effects on the female reproductive system, including stimulation of myometrial activity, relaxation of the cervix, inhibition of steroidogenesis by corpora lutea, and can potentially lyse corpora lutea.

C24H45NO8

475.6160

475.314

C, 60.61; H, 9.54; N, 2.94; O, 26.91

38562-01-5

Dinoprost; 551-11-1; Dinoprost-d4; 34210-11-2

5282415

White to off-white solid powder

531ºC at 760 mmHg

25-35ºC

289ºC

1.404

184.7

8

9

15

33

486

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].O([H])C([H])([H])C(C([H])([H])O[H])(C([H])([H])O[H])N([H])[H]

IYGXEHDCSOYNKY-RZHHZEQLSA-N

InChI=1S/C20H34O5.C4H11NO3/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;5-4(1-6,2-7)3-8/h4,7,12-13,15-19,21-23H,2-3,5-6,8-11,14H2,1H3,(H,24,25);6-8H,1-3,5H2/b7-4-,13-12+;/t15-,16+,17+,18-,19+;/m0./s1

2-amino-2-(hydroxymethyl)propane-1,3-diol;(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid

U 14585; U14585; U-14585; Dinoprost; Tromethamine; Dinoprost; Trometamol; Zinoprost; PGF2alpha THAM; Lutalyse; PGF2-alpha tham; Prostamate;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

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

DMSO: ~95 mg/mL (~199.7 mM)
Water: ~95 mg/mL
Ethanol: ~95 mg/mL

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.26 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。

---

配方 2 中的溶解度: ≥ 2.5 mg/mL (5.26 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。

---

View More

配方 3 中的溶解度: ≥ 2.5 mg/mL (5.26 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (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 900 μL 玉米油中并混合均匀。

---

配方 4 中的溶解度: 50 mg/mL (105.13 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

---

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。