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

Goat luteal cells undergo necrosis, autophagy, and endoplasmic reticulum prolapse when exposed to dinoprost (prostaglandin F2α; 1 μM) for a full day [1]. Dinoprost (1 μM) raised GRP78 and UPR sensor substantially throughout a 24-hour period.

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The ET-1-induced (10(-8) M) contraction in isolated BTM was inhibited by PGF2alpha (10(-6) M) and fluprostenol (10(-6) M). This effect was blocked by FP receptor antagonists. Carbachol-induced contraction or baseline tension was not affected by PGF2alpha or fluprostenol. In cultured TM cells, ET-1 caused a transient increase in [Ca2+]i that was reduced by PGF2alpha. No reduction occurred in the presence of the FP receptor antagonist Al-8810. Western blot analysis revealed the expression of the FP receptor in native and cultured TM. Conclusions: FP receptor agonists operate by direct interaction with ET-1-induced contractility of TM. This effect is mediated by the FP receptor. Thus, FP receptor agonists may decrease IOP by enhancing aqueous humor outflow through the TM by inhibiting ET-1-dependent mechanisms.[1]

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Corpus luteum (CL) is a transient endocrine tissue that produces progesterone for maintaining pregnancy in mammals. In addition, the regression of CL is necessary for the initiation of the estrous cycle. Extensive research has shown that the prostaglandin F2α (PGF2α) induces the regression of CL in ruminants. However, the mechanisms of endoplasmic reticulum (ER) stress and autophagy in the regression of goat CL induced by PGF2α are still unclear. In this study, ovaries of dioestrus goats and goats that were 3 months pregnant were collected to detect the location of the ER stress-related protein GRP78. The relationship between the different stages of the luteal phase of goat CL during the estrous cycle and changes in the expression of ER stress-related proteins and autophagy-related proteins was confirmed by western blot analysis. The results showed that both ER stress and autophagy were activated in the late luteal phase of the goat CL. To reveal the function of ER stress and autophagy in the CL regression process induced by PGF2α, we used 4-phenyl butyric acid (4-PBA) and chloroquine (CQ) for inhibiting ER stress and autophagy, respectively. Through the apoptotic rate detected by the flow cytometry and the expression of ER stress- and autophagy-related proteins detected by western blotting, we demonstrated that ER stress promoted goat luteal cell apoptosis and autophagy, and that apoptosis can be enhanced by the inhibition of autophagy. In addition, knockdown of EIF2S1, which blocked the PERK pathway activation, promoted apoptosis by reducing autophagy in goat luteal cells treated with PGF2α. In conclusion, our study indicates that ER stress promotes goat luteal cell apoptosis to regulate the regression of CL and activates autophagy to inhibit the goat luteal cell apoptosis via PERK signaling pathway[2].

Apoptosis analysis [1]
Cell Types: Goat luteal cells
Tested Concentrations: 1 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: Significant apoptosis rate increased (15.62±3.12%). Autophagy detection [1]
Cell Types: goat luteal cells
Tested Concentrations: 1 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: There is extensive overlap between LC3 and LAMP1 in luteal cells, and autophagic lysosomes are formed in goat luteal cells.

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Western Blot Analysis[1]
Cell Types: Goat luteal cells
Tested Concentrations: 1 μM
Incubation Duration: 24 hrs (hours)
Experimental Results: Expression of GRP78 and UPR sensors, including cleaved ATF6, phospho-EIF2S1, EIF2S1, ATF4, phospho-IRE1, autologous Phagocytosis-related intracellular protein LC3-II and pro-apoptotic factor cleaved Caspase3 were Dramatically increased.

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
AMONG COMPD OCCURRING IN SEMEN THAT ARE OF CURRENT RESEARCH INTEREST ARE PROSTAGLANDINS (25 MG/ML). /PROSTAGLANDINS/
APART FROM GENERALLY SLOW & SPECIES-DEPENDENT ISOMERIZATION, PGS E & F ARE RATHER STABLE IN BLOOD, BUT THEY ARE RAPIDLY DEGRADED & INACTIVATED BY TISSUE-BOUND ENZYMES; SOME 80-90% OR MORE IS DESTROYED DURING SINGLE PASSAGE THROUGH LIVER OR LUNGS. /PROSTAGLANDINS/
DEG OF BINDING OF PROSTAGLANDINS TO PLASMA PROTEINS APPEARS TO HAVE LITTLE INFLUENCE ON THEIR RATES OF METABOLISM & ELIMINATION. ... CLEARANCE RATES OF (3)H DID NOT CHANGE WHETHER PROSTAGLANDINS WERE ADMIN IN FREE FORM OR BOUND TO RAT PLASMA ALBUMIN. /PROSTAGLANDINS/

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Metabolism / Metabolites
...PROSTAGLANDINS ARE RAPIDLY METABOLIZED... /PROSTAGLANDINS/

Interactions
CONTRACTIONS IN RESPONSE TO PROSTAGLANDIN F2ALPHA IN HUMAN ISOLATED BRONCHIAL MUSCLE ARE INHIBITED BY FENAMATES, PHENYLBUTAZONE, &, LESS POTENTLY, ASPIRIN.

[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 F2alpha is a prostaglandins Falpha that is prosta-5,13-dien-1-oic acid substituted by hydroxy groups at positions 9, 11 and 15. It is a naturally occurring prostaglandin used to induce labor. It has a role as a human metabolite and a mouse metabolite. It is a prostaglandins Falpha and a monocarboxylic acid. It is a conjugate acid of a prostaglandin F2alpha(1-).
Dinoprost has been investigated in Headache.
Dinoprost has been reported in Homo sapiens, Cervus nippon, and other organisms with data available.
Dinoprost 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)
Prostaglandin F2alpha is a naturally occurring prostaglandin that stimulates myometrial activity, relaxes the cervix, inhibits corpus luteal steroidogenesis, and induces luteolysis by direct action on the corpus luteum. Expression of prostaglandin F2alpha (PGF2) is elevated in certain types of cancers.
A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.
See also: Dinoprost Tromethamine (has salt form).

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Mechanism of Action
...THERE IS NO SINGLE PROSTAGLANDIN RECEPTOR. ... IT IS POSSIBLE TO DEMONSTRATE CALCIUM DEPENDENCE OF DIVERSE RESPONSES TO PROSTAGLANDINS & TO OBSERVE ALTERED CALCIUM FLUXES. ...PROSTAGLANDINS MAY EITHER STIMULATE OR INHIBIT ACCUM OF CYCLIC AMP. /PROSTAGLANDINS/
RESPONSES TO PROSTAGLANDIN F2ALPHA SHOW SPECIES VARIATION, BUT VASODILATATION HAS BEEN OBSERVED FOLLOWING INJECTION INTO HUMAN BRACHIAL ARTERY OF PGF2ALPHA... SUPERFICIAL VEINS OF HAND ARE CONTRACTED BY PFG2ALPHA...
PROMPT SUBSIDENCE OF PROGESTERONE OUTPUT & REGRESSION OF CORPUS LUTEUM FOLLOWS PARENTERAL INJECTION OF PROSTAGLANDIN F2ALPHA... THIS EFFECT INTERRUPTS EARLY PREGNANCY, WHICH IS DEPENDENT ON LUTEAL RATHER THAN PLACENTAL PROGESTERONE.
OXYTOCIN & PROSTAGLANDINS AFFECT UTERINE SMOOTH MUSCLES BY DIFFERENT MECHANISMS, & THEIR EFFECTS ARE ADDITIVE. POSSIBLE ADVANTAGES OF THEIR COMBINED USE ARE BEING EXPLORED. /PROSTAGLANDINS/

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Therapeutic Uses
Abortifacient Agents, Nonsteroidal; Oxytocics
...SOME PHYSICIANS PREFER TO DEFER ABORTION UNTIL AFTER 16TH WK, WHEN INTRA-AMNIOTIC ROUTE CAN BE EMPLOYED MORE SAFELY. /DINOPROST TROMETHAMINE/
EXTRA-AMNIOTIC TECHNIQUE, WHICH IS STILL INVESTIGATIONAL, REQUIRES TRANSVAGINAL INTRAUTERINE EXTRAOVULAR PLACEMENT OF INDWELLING CATHETER. ... RESERVED FOR TERMINATION OF PREGNANCIES BETWEEN 13TH & 15TH WK... /DINOPROST TROMETHAMINE/
DOSAGE THAT ACHIEVES EFFECTIVE CONCN WITHIN MYOMETRIUM IS LOWEST WITH INTRAUTERINE ADMIN. INTRA-AMNIOTIC INSTILLATION IS ACCOMPLISHED WITH LONG SPINAL NEEDLE INSERTED TRANSABDOMINALLY INTO AMNIOTIC SAC. /DINOPROST TROMETHAMINE/
For more Therapeutic Uses (Complete) data for PROSTAGLANDIN F2ALPHA (15 total), please visit the HSDB record page.

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Drug Warnings
ASTHMATIC INDIVIDUALS ARE PARTICULARLY SENSITIVE, & PGF2ALPHA HAS CAUSED INTENSE BRONCHOSPASM.
SOME INVESTIGATORS HAVE INDICATED THAT PROSTAGLANDINS MAY SHOW NARROWER DOSE-RESPONSE RANGE FOR PRODN OF PHYSIOLOGICAL CONTRACTIONS & OCCURRENCE OF UTERINE HYPERTONUS, POTENTIAL HAZARD THAT MAY BE AVOIDED BY VERY CAUTIOUS STEPWISE INCREMENTS IN RATE OF INFUSION. /PROSTAGLANDINS/
FOR ABORTION IN 2ND TRIMESTER...RESULTS IN...FREQUENT BUT TOLERABLE SIDE EFFECTS. HOWEVER, FOR VERY EARLY ABORTION (MENSES DELAYED UP TO SEVERAL WK), RATE OF SUCCESS REPORTED IS LOW & SERIOUS SIDE EFFECTS HAVE RESULTED FROM DOSES REQUIRED. /PROSTAGLANDINS/
...CONTRAINDICATED IN ACUTE PELVIC INFLAMMATION. IT SHOULD BE USED CAUTIOUSLY IN PT WITH HISTORY OF HYPERTENSION, ASTHMA, GLAUCOMA, EPILEPSY, OR CARDIOVASCULAR DISEASE.
For more Drug Warnings (Complete) data for PROSTAGLANDIN F2ALPHA (11 total), please visit the HSDB record 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

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)