Disease relevance of fluprostenol

• Fluprostenol-induced activation was pertussis toxin resistant [1].
• Cicaprost and fluprostenol were virtually inactive; they also failed to modify copper sulphate (100 mg/kg, intragastric)-induced emesis (P>0.05), although cicaprost potentiated apomorphine (0.25 mg/kg, s.c.)-induced emesis (P<0.05) [2].
• A total of 941 mares have been treated with fluprostenol in an international trial, for various forms of infertility associated with abnormal persistence of luteal function [3].
• In addition, administration of fluprostenol, a more selective agonist at the PGF(2alpha) receptor, induced cardiac hypertrophy in rats [4].
• Time between birth and first suckling, body weight, rectal temperature, pulse rate, and respiratory rate at birth and serum IgG concentration 24 hours after birth were not different between crias born after fluprostenol treatment and crias born to control alpacas [5].

High impact information on fluprostenol

• The prostaglandin F receptor (FP) selective agonist, fluprostenol, was the most potent agonist tested, significantly inhibiting incorporation of [3H]proline into both collagen and noncollagen protein at 10(-11) M, with more than 90% inhibition of collagen synthesis at 10(-8) M [6].
• However, supplementing stretched, COX2-/- myoblasts with prostaglandin E2 or fluprostenol increased proliferation [7].
• These data suggest that fluprostenol and oxytocin activate PLC-beta rather than PLC-gamma isoforms [8].
• PGF2 alpha and fluprostenol activated PLC (determined by measuring the formation of inositol phosphates) and increased [Ca2+]i in a concentration-dependent manner [8].
• However, neither fluprostenol nor oxytocin stimulated tyrosine phosphorylation, but the effects of both agonists were inhibited after protein kinase C stimulation [8].

Biological context of fluprostenol

• At doses up to 100 microg, fluprostenol did not decrease intraocular pressure but did reduce pupil diameter [9].
• Doses of fluprostenol 100-fold larger were necessary to increase uterine contractions [10].
• (3) During luteolysis, short and frequently occurring phases of activity were propagated between the two electrodes on one uterine horn; a similar pattern also occurred between 1 and 3 h after injection of fluprostenol [11].
• Insemination during oestrus and injection of fluprostenol during dioestrus caused a marked and prolonged increase in myometrial electrical activity [11].
• In the majority, parturition was induced with oxytocin and/or fluprostenol; the remainder were allowed to foal spontaneously [12].

Anatomical context of fluprostenol

• Immunogold labeling of calvariae revealed that treatment with Flup for 3 h caused a transition of FGF expression from matrix to cells and an increase in cytoplasmic labeling for FGF-2 protein in periosteal cells and in osteoblasts [13].
• We have shown previously that treatment of 3T3-L1 preadipocytes with prostaglandin F2alpha (PGF2alpha) and fluprostenol, a prostanoid FP2 receptor (FP receptor) agonist, inhibited adipocyte differentiation [14].
• After treatment with Flup for 24 h, nuclear labeling was marked in periosteal cells and in osteoblasts, and a further increase in cytoplasmic labeling for FGF-2 was noted in osteocytes, periosteal cells, and osteoblasts [13].
• 1. Prostaglandin F2 alpha (PGF2 alpha) and its synthetic analogue, fluprostenol, potently relaxed the precontracted isolated jugular vein of the rabbit (RJuV) [15].
• Pretreatment of Swiss 3T3 cells with either 1 microM PGF(2alpha) 1-OH or PGF(2alpha) 1-OCH(3) did not attenuate Ca(2+) signal responses produced by PGF(2alpha) or fluprostenol [16].

Associations of fluprostenol with other chemical compounds

• Specific [3H]PGF2alpha binding was potently displaced by FP-selective agents such as fluprostenol, PHXA85 and cloprostenol with nanomolar affinities (n = 3-25), but weakly (Kis > 1 microM) by other PGs showing high selectivity for other PG receptor subtypes mentioned above [17].
• Using [3H]PGF2 alpha, binding of PGs showed the rank order of fluprostenol > PhXA70 > PGF2 alpha > or = PhXA85 > PGD2 > PGE2 [18].
• Uterine electromyography was performed by means of chronically implanted surface electrodes in 3 Pony mares during spontaneous oestrous cycles and following luteolysis induced by a prostaglandin analogue (fluprostenol) [11].
• OBJECTIVE: To evaluate use of fluprostenol, dexamethasone, and oxytocin for induction of parturition in alpacas, and to determine viability of the newborn crias [5].
• A clinical trial involving 359 mares was conducted to ascertain the clinical value of a synthetic prostaglandin analogue (fluprostenol, ICI-81,008) structurally related to PGF2oc for treating mares in prolonged dioestrus [19].

Gene context of fluprostenol

• Finally, we tested the effect of RGS-2 overexpression on PTH- and fluprostenol-induced interleukin (IL)-6 promoter activity in MOB cells [20].
• Erk activity and colony size were increased by cotreatment of JB6 cells with epidermal growth factor (EGF) and fluprostenol to a greater extent than with either treatment alone, whereas the cotreatment effect on colony number appeared to be simply additive [21].
• 4. Fluprostenol had no effect on the human umbilical artery at concentrations up to 17 microM suggesting the absence of FP receptors [22].
• We have previously reported that prostaglandin F(2alpha) (PGF(2alpha)) and its selective agonist fluprostenol increase basic fibroblast growth factor (FGF-2) mRNA and protein production in osteoblastic Py1a cells [23].
• Fluprostenol, a selective FP receptor agonist, could mimic PGF2 alpha-induced effect on ICAM-1 expression [24].

Analytical, diagnostic and therapeutic context of fluprostenol

• By immunofluorescence microscopy, Flup increased perinuclear staining for FGF-2 protein at 6 h and nuclear labeling at 24 h [13].
• Fluprostenol in mares: clinical trials for the treatment of infertility [3].
• Some 263 mares (73.3%) displayed oestrus within 5 days of a first intramuscular injection of 250 mug fluprostenol and, of those mares later examined for pregnancy, 108 (40%) were found to have conceived during the first induced oestrus [19].
• Use of short high-performance liquid chromatography columns and tandem-mass spectrometry for the rapid analysis of a prostaglandin analog, fluprostenol, in rat plasma [25].

References