Mating increases plasma levels of prostaglandin F2 alpha in female garter snakes

Plasma levels of prostaglandin F2 alpha (PGF2 alpha) in female red-sided garter snakes (Thamnophis sirtalis parietalis) were measured at intervals after mating or exposure to males. PGF2 alpha levels increased significantly within 15 minutes of mating and peaked 6-24 hr after mating. Females that did not mate, but received similar amounts of male courtship, had levels of PGF2 alpha significantly lower than those of females that mated. These results extend previous findings that unmated female garter snakes injected with PGF2 alpha exhibit sexual behavior characteristic of females that have mated. Together these data indicate that female garter snakes elaborate PGF2 alpha in response to stimuli associated with mating and that PGF2 alpha has a functional role in inducing post-mating declines in sexual behavior of this species.     

Radioimmunoassays of prostaglandin F2α and prostaglandin F2α-main urinary metabolite with prostaglandin-I-tyrosine methylester amide

Radioimmunoassays for measuring prostaglandin F_2α (PGF_2α) and 5α, 7α-dihydroxy-11-keto tetranorprosta-1,16-dioic acid, PGF_2α-main urinary metabolite (PGF_2α-MUM), with ¹²⁵I-tyrosine methylester amide (TMA) of PGF_2α and PGF_2α-MUM were developed.Antibody to PGF_2α was produced in rabbits immunized with conjugates of PGF_2α coupled to bovine serum albumine. Antibody to PGF_2α-MUM was also produced in rabbits immunized with conjugates of PGF_2α-MUM coupled to bovine serum albumin.PGF_2α-¹²⁵I-TMA had an affinity to antiserum to PGF_2α. PGF_2α-MUM-¹²⁵I-TMA also responded to antiserum to PGF_2α-MUM.     

The enzymatic conversion of prostaglandin D2 to prostaglandin F2α

Prostaglandins E₂ and D₂ were both converted to prostaglandin F_2α (9α, 11α) by an enzyme present in sheep blood. Neither the 9β, 11α epimer nor the 9α, 11β epimer was produced from PGE₂ or PGD₂ respectively. The rate of reduction was measured using isotope dilution (D₄ PGF_2α) and multiple-ion detection gas chromatography-mass spectrometry.     

6 keto prostaglandin F1α plasma levels in aminonucleoside nephrosis in the rat

Levels of 6 keto Prostaglandin F_1α were measured by radioimmunoassay in rats with nephrotic syndrome induced by the intraperitoneal administration of aminonucleoside of puromycin. The plasma levels were found to be significantly elevated in nephrotic as compared to control rats (p < 0.01).     

Urinary excretion of prostaglandin E2 and prostaglandin F2α in potassium-deficient rats

Potassium-deficiency was induced in rats by dietary deprivation of potassium. The animals became polyuric and urine osmolality decreased more then three-fold compared to controls. Urinary excretion of prostaglandin E₂ (PGE₂) and prostaglandin F_2α (PGF_2α) did not increase during 2 weeks of potassium depletion. Partial inhibition of renal prostaglandin synthesis by meclofenamate did not increase the urine osmolality after water deprivation. These results make unlikely the hypothesis that the polyuria of potassium-deficiency, is the result of enhanced renal synthesis of prostaglandins with subsequent antagonism of the hydro-osmotic effect of vasopressin. Male animals consistently excreted less PGE₂ than female animals.     

Intra-amniotic prostaglandin F2α and urea for abortion

Prostaglandin F_2α (PGF_2α) 20 mg combined with urea 80 g was injected intra-amniotically in 20 patients to induce mid-trimester abortion. Abortion resulted in all subjects within 24 hours in a mean time of 12 hours 38 minutes (range 5 hours 50 minutes to 20 hours 45 minutes).Plasma sex steroids were evaluated before and hourly for 5 hours after the injection. A progressive decline in levels occurred with time. Decreases in plasma progesterone, estrone, estradiol and estriol were significant as soon as one hour after injection.Gastrointestinal side effects occurred with a greater frequency than when a comparable dose of PGF_2α is given alone and 2 patients had small cervical lacerations requiring suture. Further studies are indicated to establish whether a lower dose of PGF_2α will be associated with fewer side effects and be as effective.     

Intrauterine instillation of prostaglandin F2α in early pregnancy

Intrauterine PGF_2α (5mg) was administered for termination of early pregnancy in 14 healthy volunteers. With 11 complete abortions, the efficiency rate of this technique is below conventional methods. In addition, the incidence of infection was high occurring in 12 out of 14 subjects. Because of persistent bleeding, six patients underwent a dilatation and curettage. Other significant side effects included transient hypertension, pain, nausea and restlessness. In the patients with a complete abortion, the mean plasma progesterone concentration fell 37% after 8 hours post PGF_2α instillation and 90% 14 days later. The mean plasma estradiol-17β fell 26% over the initial eight hour period and 75% over the next 14 days.     

Termination of pregnancy in cats with prostaglandin F2α

Two subcutaneous injections of Prostaglandin F_2α THAM salt 24 hours apart terminated pregnancies in cats after the 40th day of gestation. Injections of 0.50 or 1.00 mg. PGF_2α THAM salt/Kg. body weight were the most effective in terminating pregnancies. Parturition or abortion occurred within 24 hours after the initial injection in 9 cats and after the 2nd injection in 4 cats.     

Cardiac arrhythmias induced by prostaglandin F2α in cats

Intravenous administration of prostaglandin F_2α results in transient episodes of sinus bradycardia in anesthetized cats. In addition, ventricular bigeminy was observed in approximately 40% of those cats anesthetized with pentobarbital (36 mg/kg) and 58% of those anesthetized with chloralose (70 mg/kg). This arrhythmogenic effect of PGF_2α is abolished following bilateral vagotomy, indicating that the arrhythmias are most likely due to a marked stimulation of vagal tone in this species.     

Stereospecificity of enzymatic reduction of prostaglandin E2 to F2α

Antibodies directed toward PGF_2β were prepared in rabbits. The serologic specificity of the immune reaction was determined by inhibition of sodium borohydride-reduced (³H) PGE₂ anti-PGF_2β binding by several prostaglandins. The antibodies to PGF_2β recognize the β-hydroxyl configuration in the cyclopentane ring of PGF_2β. With the use of both anti-PGF_2α and anti-PGF_2β, the product of PGE₂ reduction by 9-ketoreductase purified from chicken heart was identified as PGF_2α. Guinea pig liver and kidney homogenates were examined for PGE 9-ketoreductase activity. Although enzyme activity was present, no evidence of PGF_2β production was found.     

Intracellular recording of cerebral cortical actions of prostaglandin F2α (PGF2α)

Our reported data on the cortical inhibitory actions of prostaglandin F_2α (PGF_2α) and the diversity of data in the literature on cerebral PG actions are examined here in the light of intracellular recording which provides the requisite membrane data for the first time. Thus, 1) intracellular recording from the cat cerebral cortex is obtained for the actions of PGF_2α and for norepinephrine (NE) and serotonin (5HT). 2) The parallel changes in firing and polarization and the simultaneous transmembrane conductance changes are qualitatively identical for PGF_2α, NE and 5HT. 3) The reduction in firing accompanied by hyperpolarization indicates that PGF_2α, NE and 5HT all inhibit these cells. 4) The ionic species responsible for this inhibition is such that it increased the transmembrane resistance, and this was true for all three. 5) The changes in membrane parameters, identical in direction for PGF_2α and NE, but stronger for the latter, constitute conditions that can lead to competitive inhibition and therefore conote, presumably, actions at the same or related receptors. Such competition with evoked cortical field potentials is shown in the preceding paper.     

Viroimmunoassay of prostaglandin F2α at the picogram level

A viroimmunoassay of PG F_2α is presented here. By a modification of the technique used by Dray et al. (3), it allowed us to measure as low as one picogram of PG F_2α. It seems that such a sensitive assay might be usefull for many purposes in the prostaglandin field.     

The excretion of prostaglandin F2α in milk of cows

Prostaglandin F_2α (PGF_2α) was measured by immunoassay in plasma and milk of four cows (six experiments). After 30 mg PGF_2α im, plasma PGF_2α peaked at 15 minutes (2.4 ± 0.7 ng/ml) and declined toward basal values by 3 hours; maximum milk PGF_2α (0.91 ± 0.12 ng/ml) occurred at 1 hour. The average excretion rate in milk was 2.9 μg/day 0.9 μg (0.003%) of which was due to the 30 mg PGF_2α injected. In six non-pregnant control cows, daily changes of milk PGF_2α and progesterone were not consistently related.     

Metabolism of prostaglandin F1α in the pulmonary circulation

³H_5,6-Prostaglandin F_1α is largely eliminated from the circulation during a single passage through the pulmonary vascular bed. Its elimination requires cellular uptake. The volume of distribution and the mean transit time of the radioactivity are greater than those of an intravascular marker, blue dextran. The lungs retain 25–30% of the radioactivity, most in the form of a metabolite less polar than PGF_1α itself. The pulmonary venous effluent contains the same metabolite along with some unmetabolized PGF_1α. The metabolite can be distinguished from prostaglandins of the A, B, D, E and F series. It is reduced on reaction with borohydride, but reduction does not yield PGF_1α. NaOH has no effect on the metabolite, a finding that rules out the presence of a β-hydroxy-ketone configuration of the ring structure. The chromatographic behavior of the metabolite and its reaction with borohydride are those expected of 9,11-hydroxy-15-ketoprostanoic acid.     

Concentrations of prostaglandin F2α in the pig oviductal fluid

Oviductal fluid was continuously collected from cycling, unrestrained gilts during late proestrus, standing heat and early luteal pahse. Collection was performed via cannulae exteriorized to single vented collection tubes attached to the skin. In some cases one of the oviducts was transected at isthmic level to compare fluid production rates with those of the contralateral intact tube. A consistently elevated fluid production was observed during proestrus and standing heat, being highest at the second day of the cycle, there- after decreasing. No significant differences were seen between daily collection rates from right or left nor between intact and isthmic transected oviducts. Levels of PGF_2α were determined by RIA in the collected samples. Relatively large day to day fluctuations in PGF_2α values were evident and a consistent relatinship was found between concentration and the stage of the estrous cycle. The highest PGF_2α mean values (up to 50 ng/ml fluid) were also found on the second day of standing heat, concurrently periovulatory.     

Prostaglandin F2α increases responsiveness of pulmonary airways in dogs

We studied the effect of prostaglandin F_2α (PGF_2α) on the responsiveness of pulmonary airways in dogs. Airway responsiveness was assessed by determining the bronchoconstrictor response to increasing concentrations of acetylcholine aerosol delivered to the airways. In each of five dogs, we determined responsiveness during treatment with physiologic saline, histamine, or PGF_2α aerosols. The doses of histamine and PGF_2α were determined by establishing the largest dose of each which could be given to the dog without causing bronchoconstriction (subthreshold doses). We found that airway responsiveness was not significantly different during histamine treatment than after saline, however, responsiveness increased during treatment with PGF_2α. In addition, the hyperresponsiveness induced by PGF_2α was prevented by pretreatment with the ganglion blocking drug hexamethonium (5 mg/kg given intravenously). The results show that PGF_2α specifically increases the responsiveness of pulmonary airways in doses that do not cause bronchoncostriction, and suggest that the hyperresponsiveness involves a neural mechanism such as increased responsiveness of airway sensory nerves.     

Prostaglandin F2α levels in the human ovarian follicle

Prostaglandin F_2α concentrations measured in ovarian follicular fluid from thirty-four patients rose significantly during the pre-ovulatory phase, reaching a peak at day 14 and falling after mid-cycle. These findings provide evidence in women to support a role for prostaglandins, acting at the follicular level, in the process of ovulation.     

Release of prostaglandin F2α during the bovine peripartal period

Progesterone, estrone and 15-keto-13,14-dihydro-PGF_2α levels were determined in the peripheral blood circulation during the peripartal period in 12 cows. Plasma concentrations of progesterone showed a gradual and continuous decrease during the last 60 days before parturition. This gradual decrease was followed by an abrupt decline in the progesterone concentration occurring 24–48 hours before delivery. The plasma levels of estrone started to increase about 30 days prior to parturition with high concentrations attained during the last days of pregnancy. After delivery the estrone content decreased to baseline levels. Increased levels of the PGF_2α metabolite were recorded 24–48 hours before parturition. These increased PGF_2α metabolite levels occurred before or in conjunction with prepartum luteolysis. Prostaglandin metabolite levels remained high during parturition and returned to baseline 10–20 days after delivery.     

15-methylation augments the cardiovascular effects of prostaglandin F2α

Intramuscular injection of the 15-methyl analogue of prostaglandin F_2α (15-me-PGF_2α) is being used to initiate second trimester abortion. The natural prostaglandin F_2α (PGF_2α) is a known pulmonary pressor agent but there is little information about the cardiovascular effects of the analogue. Consequently, we compared the hemodynamic responses to the two forms in twenty-three anesthetized dogs. Given I.M. or I.V. 15-me-PGF_2α produced a greater and more sustained rise in pulmonary arterial pressure than PG F_2α. Intramuscular 15-me-PGF_2α also elicited a more prolonged increase in pulmonary vascular resistance than prostaglandin F_2α given I.M. or I.V. The methyl analogue (I.M. or I.V.) causes a greater initial fall in systemic arterial oxygen tension and cardiac output, and a greater increase in systemic resistance than I.M. PG F_2α Breathlessness seen during abortion induced by prostaglandin F_2α or its methyl analogue may be caused by acute pulmonary hypertension in addition to bronchoconstriction.