cloprostenol and fluprostenol

Topics: Abortion, Induced; Animals; Animals, Domestic; Cattle; Cloprostenol; Dinoprost; Female; Goats; Horses; Luteolytic Agents; Pregnancy; Prostaglandins; Prostaglandins F; Prostaglandins F, Synthetic; Sheep; Swine

Although prostanoids are known to be involved in regulation of the spontaneous beating rate of cultured neonatal rat cardiomyocytes, the various subtypes of prostanoid receptors have not been investigated in detail. In our experiments, prostaglandin (PG)F(2α) and prostanoid FP receptor agonists (fluprostenol, latanoprost and cloprostenol) produced a decrease in the beating rate. Two prostanoid IP receptor agonists (iloprost and beraprost) induced first a marked drop in the beating rate and then definitive abrogation of beating. In contrast, the prostanoid DP receptor agonists (PGD(2) and BW245C) and TP receptor agonists (U-46619) produced increases in the beating rate. Sulprostone (a prostanoid EP(1) and EP(3) receptor agonist) induced marked increases in the beating rate, which were suppressed by SC-19220 (a selective prostanoid EP(1) antagonist). Butaprost (a selective prostanoid EP(2) receptor agonist), misoprostol (a prostanoid EP(2) and EP(3) receptor agonist), 11-deoxy-PGE(1) (a prostanoid EP(2), EP(3) and EP(4) receptor agonist) did not alter the beating rate. Our results strongly suggest that prostanoid EP(1) receptors are involved in positive regulation of the beating rate. Prostanoid EP(1) receptor expression was confirmed by western blotting with a selective antibody. Hence, neonatal rat cardiomyocytes express both prostanoid IP and FP receptors (which negatively regulate the spontaneous beating rate) and prostanoid TP, DP(1) and EP(1) receptors (which positively regulate the spontaneous beating rate).

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Animals, Newborn; Blotting, Western; Cells, Cultured; Cloprostenol; Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; Dinoprostone; Dose-Response Relationship, Drug; Epoprostenol; Hydantoins; Iloprost; Latanoprost; Myocytes, Cardiac; Prostaglandin D2; Prostaglandins F, Synthetic; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin; Receptors, Prostaglandin E, EP1 Subtype; Receptors, Thromboxane

The pharmacological properties of [(3)H]-prostaglandin E(2) ([(3)H]-PGE(2)) binding to washed homogenates of hamster uterus were determined. Scatchard analysis of competition data yielded dissociation constants (K(d)s) of 30.9 +/- 5.6 nM (n = 3) and apparent receptor density (B(max)) of 25.25 +/- 1.89 pmol g(-1) wet weight tissue (74 +/- 8% specific binding). Competition studies yielded the following affinity parameters (K(i)) for various prostanoids: GR63799X = 13 4 nM; PGE(2) = 17 +/- 3 nM; sulprostone = 64 +/- 5 nM; enprostil = 67 +/- 3 nM; misoprostol = 124 +/- 15 nM; cloprostenol = 187 +/- 33 nM; carba-prostacyclin = 260 +/- 167 nM; iloprost = 555 +/- 162 nM; PGF(2 alpha) = 767 +/- 73 nM; PGD(2) > 3560 nM; fluprostenol = 11 790 +/- 2776 nM; RS93520 = 21 558 +/- 14 228 nM. These data closely matched the pharmacological profile of previously described EP(3) receptors such as in bovine corpus luteum (BCLM) and the cloned mammalian EP(3) receptors. The high correlation between the current hamster uterus pharmacology data vs the EP(3) receptor binding in BCLM (r = 0.94; P < 0.0001), vs cloned human EP(3) receptor (r = 0.94, P < 0.0001), vs the cloned mouse EP(3) receptor binding (r = 0.78; P < 0.002), vs cloned rat EP(3) receptor (r = 0.9, P < 0.0004), and vs EP(3) receptor-mediated functional responses (r = 0.72, P < 0.02) substantiated the conclusion that the hamster uterus contains EP(3) receptor binding sites.

Topics: Animals; Binding Sites; Biphenyl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cattle; Cloprostenol; Cricetinae; Dinoprost; Dinoprostone; Enprostil; Epoprostenol; Fatty Acids, Unsaturated; Female; Hydantoins; Hydrazines; Iloprost; Latanoprost; Misoprostol; Prostaglandins; Prostaglandins E, Synthetic; Prostaglandins F, Synthetic; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP3 Subtype; Tritium; Uterus

Prostaglandin F2alpha inhibits adipose differentiation of primary culture of adipocyte precursors and of the adipogenic cell line 1246 in defined medium. In the present paper, we investigated the effect of FP receptor agonists cloprostenol and fluprostenol on the differentiation of newborn rat adipocyte precursors in primary culture. The results show that cloprostenol and fluprostenol are very potent inhibitors of adipose differentiation. Dose response studies indicate that both agonists are more potent than PGF2alpha in inhibiting adipocyte precursors differentiation. 50% inhibition of adipose differentiation was observed at a concentration of 3 x 10(-12) M for cloprostenol and 3 to 10 x 10(-11) M for fluprostenol respectively whereas the PGF2alpha concentration required to elicit the same effect was 10(-8) M. In contrast compounds structurally related to PGE2 such as 17-phenyl trinor PGE2 had no effect on adipose differentiation except when added at a 10,000-fold higher concentration.

Topics: Adipocytes; Animals; Cell Differentiation; Cell Line; Cloprostenol; Culture Media; Glycerolphosphate Dehydrogenase; Prostaglandins F, Synthetic; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin

Three experiments were conducted to test the abortifacient effects of PGF2 alpha analogues on mares during midgestation (average gestation length 141.5 days). The progesterone concentration was measured by radioimmunoassay. In experiment 1. five mares received an injection of PGF2 alpha analogue (fluprostenol: 500 micrograms intramuscularly) and a second injection either at 24, 48, of 72 h. Although the progesterone concentration decreased (P less than 0.05) an average of 44 per cent in 24 h, none of the pregnancies were terminated. In experiment 2, beginning at least 10 days after experiment 1, the same five mares were given PGF2 alpha analogue as follows: 250 micrograms intravaginally and 500 micrograms intramuscularly. The treatment was repeated 48 h later. Progesterone concentrations had not increased since experiment 1 and did not decrease during the 48 h following either injection. In experiment 3, six mares (average gestation length 162 days) were treated every 6 or 12 h with PGF2 alpha analogue (cloprostenol: 375 micrograms) until expulsion of the fetus occurred at 47 +/- 25 h after the initial injection; the mares received an average of 5 treatments. The progesterone concentration averaged 22 +/- 7 ng/ml before the initial PGF2 alpha treatment, decreased (P less than 0.05) to 8.4 +/- 2.7 ng/ml by 12 h before expulsion and 1-8 +/- 0.4 ng/ml 12 h after fetal expulsion. The progesterone concentration remained below 1.0 ng/ml for the next 4 days. However, only one of six mares exhibited estrual behavior after induced abortion.

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Animals; Cloprostenol; Estrus; Female; Horses; Luteolytic Agents; Pregnancy; Progesterone; Prostaglandins F, Synthetic

Topics: Cloprostenol; Corpus Luteum; Female; Humans; In Vitro Techniques; Progesterone; Prostaglandins F, Synthetic; Time Factors