-
British Journal of Pharmacology Apr 19801 The following experiments were undertaken to confirm that prostaglandin is necessary for noradrenaline to exert its full vasoconstrictor effect in rat mesenteric blood...
1 The following experiments were undertaken to confirm that prostaglandin is necessary for noradrenaline to exert its full vasoconstrictor effect in rat mesenteric blood vessels. Prostaglandin release and inactivation were also studied. 2 The cyclo-oxygenase inhibitor, 5, 8, 11, 14-eicosatetraynoic acid caused a significant depression of the concentration-effect curve to noradrenaline. As with indomethacin, responses were restored to control levels by prostaglandin E2 (PGE2) but PGE2 did not restore responses to noradrenaline depressed by papaverine. 3 PGE2-like activity was released from tissues at rest, equivalent to 50 +/- 20 pg PGE2/min. The substance was probably a stable prostaglandin since activity remained on acidifying and extracting into chloroform. The increase in release stimulated by noradrenaline was reduced below resting values by indomethacin. 4 There was a net loss of 7 +/- 1 and 1 +/- 0.2 ng PGE2/min from tissues perfused with 40 and 4 ng/min PGE2 respectively. No uptake occurred at lower PGE2 perfusion rates. 5 When indomethacin was used to depress responses to noradrenaline 15(S)-15-methyl PGE2 methyl ester was 12 times more potent than PGE2 in restoring responses to control values. The cyclic endoperoxide analogue U-46619 caused only partial restoration of indomethacin-depressed responses to noradrenaline but increased perfusion pressure at 2 ng/ml and above. 6 The results confirm that endogenous prostaglandin release, possible of PGE2, is obligatory to the full vasoconstrictor effect of noradrenaline. Noradrenaline increases the amount of prostaglandin released which may be taken up and inactivated by 15-hydroxy prostaglandin dehydrogenase or beta-oxidase. U-46619 may mimic both PGE2 and thromboxane A2.
Topics: 5,8,11,14-Eicosatetraynoic Acid; Animals; Blood Vessels; In Vitro Techniques; Indomethacin; Mesentery; Prostaglandin Endoperoxides, Synthetic; Prostaglandins; Prostaglandins E; Rats; Vasoconstrictor Agents
PubMed: 7378646
DOI: 10.1111/j.1476-5381.1980.tb10869.x -
Journal of Visualized Experiments : JoVE Jun 2013Caenorhabditis elegans is emerging as a powerful animal model to study the biology of lipids(1-9). Prostaglandins are an important class of eicosanoids, which are lipid...
Caenorhabditis elegans is emerging as a powerful animal model to study the biology of lipids(1-9). Prostaglandins are an important class of eicosanoids, which are lipid signals derived from polyunsaturated fatty acids (PUFAs)(10-14). These signalling molecules are difficult to study because of their low abundance and reactive nature. The characteristic feature of prostaglandins is a cyclopentane ring structure located within the fatty acid backbone. In mammals, prostaglandins can be formed through cyclooxygenase enzyme-dependent and -independent pathways(10,15). C. elegans synthesizes a wide array of prostaglandins independent of cyclooxygenases(6,16,17). A large class of F-series prostaglandins has been identified, but the study of eicosanoids is at an early stage with ample room for new discoveries. Here we describe a procedure for extracting and analyzing prostaglandins and other eicosanoids. Charged lipids are extracted from mass worm cultures using a liquid-liquid extraction technique and analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The inclusion of deuterated analogs of prostaglandins, such as PGF2 α-d4 as an internal standard is recommended for quantitative analysis. Multiple reaction monitoring or MRM can be used to quantify and compare specific prostaglandin types between wild-type and mutant animals. Collision-induced decomposition or MS/MS can be used to obtain information on important structural features. Liquid chromatography mass spectrometry (LC-MS) survey scans of a selected mass range, such as m/z 315-360 can be used to evaluate global changes in prostaglandin levels. We provide examples of all three analyses. These methods will provide researchers with a toolset for discovering novel eicosanoids and delineating their metabolic pathways.
Topics: Animals; Caenorhabditis elegans; Chromatography, Liquid; Eicosanoids; Prostaglandins; Tandem Mass Spectrometry
PubMed: 23851568
DOI: 10.3791/50447 -
European Journal of Biochemistry Jul 1988In isolated rat liver perfused at constant pressure perivascular nerve stimulation caused an increase of glucose and lactate output and a reduction of perfusion flow....
In isolated rat liver perfused at constant pressure perivascular nerve stimulation caused an increase of glucose and lactate output and a reduction of perfusion flow. The metabolic and hemodynamic nerve effects could be inhibited by inhibitors of prostanoid synthesis, which led to the suggestion that the effects of nerve stimulation were, at least partially, mediated by prostanoids [Iwai, M. & Jungermann, K. (1987) FEBS Lett. 221, 155-160]. This suggestion is corroborated by the present study. 1. Prostaglandin D2, E2 and F2 alpha as well as the thromboxane A2 analogue U46619 enhanced glucose and lactate release and lowered perfusion flow similar to nerve stimulation. 2. The extents, the kinetics and the concentration dependencies of the metabolic and hemodynamic actions of the various prostanoids were different. Prostaglandin F2 alpha and D2 caused relatively stronger changes of metabolism, while prostaglandin E2 and U46619 had stronger effects on hemodynamics. Prostaglandin F2 alpha elicited greater maximal alterations than D2 with similar half-maximally effective concentrations. Prostaglandin F2 alpha mimicked the nerve actions on both metabolism and hemodynamics best with respect to the relative extents and the kinetics of the alterations. 3. The hemodynamic effects of prostaglandin F2 alpha could be prevented completely by the calcium antagonist nifedipine without impairing the metabolic actions of the prostanoid. Apparently, prostaglandin F2 alpha influenced metabolism directly rather than indirectly via hemodynamic changes. The present results, together with the previously described effects of prostanoid synthesis inhibitors, suggest that prostanoids, probably prostaglandin F2 alpha and/or D2, could be involved in the actions of sympathetic hepatic nerves on liver carbohydrate metabolism. Since prostanoids are synthesized only in non-parenchymal cells, nervous control of metabolism appears to depend on complex intra-organ cell-cell interactions between the nerve, non-parenchymal and parenchymal cells.
Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Dinoprost; Dinoprostone; Electric Stimulation; Glucose; Hemodynamics; Lactates; Lactic Acid; Liver; Male; Norepinephrine; Perfusion; Prostaglandin D2; Prostaglandin Endoperoxides, Synthetic; Prostaglandins D; Prostaglandins E; Prostaglandins F; Rats; Rats, Inbred Strains; Sympathetic Nervous System; Thromboxane A2
PubMed: 3165341
DOI: 10.1111/j.1432-1033.1988.tb14164.x -
Fertility and Sterility Aug 1973
Topics: Abortion, Therapeutic; Adolescent; Adult; Amniocentesis; Amnion; Curettage; Female; Humans; Infusions, Parenteral; Injections; Injections, Intravenous; Labor, Obstetric; Meperidine; Methods; Oxytocin; Pregnancy; Prostaglandins; Seaweed; Uterine Hemorrhage; Vomiting
PubMed: 4718913
DOI: No ID Found -
Journal of Medicinal Food Jan 2022Previously, we demonstrated that extracts of the ripe fruit (rPM) and unripe fruit (uPM) of (Siebold) Siebold & Zucc. and citric acid have a laxative effect, which is...
Citric Acid-Enriched Extract of Ripe (Siebold) Siebold & Zucc. Induces Laxative Effects by Regulating the Expression of Aquaporin 3 and Prostaglandin E in Rats with Loperamide-Induced Constipation.
Previously, we demonstrated that extracts of the ripe fruit (rPM) and unripe fruit (uPM) of (Siebold) Siebold & Zucc. and citric acid have a laxative effect, which is at least partially mediated by the increase in fecal parameters as seen in the low-fiber diet-induced constipation model rats. This study aims at investigating the laxative effects of citric acid-enriched aqueous extracts of rPM, uPM, and its active compounds, such as citric acid and malic acid, on loperamide-induced constipation rat models. Animal studies were conducted with loperamide-induced constipation animal models. The results showed that rPM and citric acid, the major organic acid compounds, significantly improved stool parameters (number, weight, and water content of the stools) generated in loperamide-induced constipation rats, without adverse effects of diarrhea. The gastrointestinal (GI) motility was activated fully in the rPM- and citric acid-treated rats than in rats treaded with loperamide alone. In addition, when rPM and citric acid were added to RAW264.7 cells and used to treat loperamide-induced constipation model rats, the secretion of prostaglandin E (PGE) increased significantly in cells and tissue. Furthermore, rPM and citric acid decreased the expression of the aquaporin 3 (AQP3) in the rat colons. Our results demonstrated that rPM and citric acid, the major organic acid compound in rPM, can effectively promote defecation frequency and regulate PGE secretion and AQP3 expression in the colon, providing scientific evidence to support the use of rPM as a therapeutic application.
Topics: Animals; Aquaporin 3; Citric Acid; Constipation; Laxatives; Loperamide; Prostaglandins; Prostaglandins E; Prunus; Rats
PubMed: 35029511
DOI: 10.1089/jmf.2021.K.0138 -
British Journal of Pharmacology Dec 19771 Prostaglandin-like material was extracted from muscle and mucosa of surgically removed human stomach, ileum and colon and assayed against prostaglandin E(2) on strips...
1 Prostaglandin-like material was extracted from muscle and mucosa of surgically removed human stomach, ileum and colon and assayed against prostaglandin E(2) on strips of rat gastric fundus. Superfused human isolated gastric mucosa released prostaglandin-like material and release was increased by stretching or clamping the tissue.2 The relative amounts of extracted biological activity were broadly as follows: gastric antral mucosa > colon muscle > gastric body mucosa approximately ileal mucosa > colon mucosa approximately gastric muscle approximately ileal muscle.3 Prostaglandin E and F were tentatively identified by chromatography and sensitivity to inactivation by alkali.4 Prostaglandin E apparently contributed most to the biological activity, possibly because the assay tissue is more sensitive to prostaglandin E than to F. Chromatography of gastric body mucosal extracts located material running with prostaglandin E(2) and a little with E(1). Colonic muscle and mucosal extracts contained material with R(F) values of prostaglandins E(1), E(2), E(3) and F(1a), whereas F(2a) and F(3a)-like substances were found only in the mucosa. The proportions of prostaglandin F varied between specimens.5 The amount of extracted prostaglandin-like activity was increased by adding cofactors and arachidonic acid, and lessened by homogenization with acid-ethanol.6 The type and amount of activity generated from arachidonic acid by partly purified colonic mucosal prostaglandin synthetase depended on the substrate concentration.7 The possible relationships of prostaglandins to mucus secretion and other physiological and pathological gut functions are discussed.
Topics: Biological Assay; Colon; Digestive System; Humans; Intestine, Small; Prostaglandins; Rectum; Stomach
PubMed: 597665
DOI: 10.1111/j.1476-5381.1977.tb07551.x -
Indian Journal of Ophthalmology May 2022The objective of this meta-analysis was to evaluate the effect of prostaglandin analogues (PGA) on central corneal thickness (CCT) in patients with glaucoma. Key... (Meta-Analysis)
Meta-Analysis Review
The objective of this meta-analysis was to evaluate the effect of prostaglandin analogues (PGA) on central corneal thickness (CCT) in patients with glaucoma. Key electronic databases were searched for randomized controlled trials (RCTs) involving the CCT effects of prostaglandin use for glaucoma. Primary outcome measures were the mean difference in the CCT measurement from baseline to the last available assessment. Intraocular pressure and other corneal changes were recorded as secondary. Efficacy estimates were measured by their weighted mean difference (WMD) with 95% confidence intervals (CI's) by using the random-effects model for primary and secondary outcomes Trial sequential analysis was used to determine if the current evidence was sufficient and conclusive. Eight RCTs met our inclusion criteria. A total of 879 patients were included. The overall effect showed that PGA's had a significant CCT lowering effect (WMD = -7.04, 95%CI: -10.07 to -4.00, P < 0.00001). We pooled results of 5 RCT's on Travoprost (WMD = -10.44, 95%CI: -16.80 to -4.08, P = 0.001), seven trials on Latanoprost (WMD = -4.73, 95% CI: -9.70 to 0.25, P = 0.06), and three trials on Bimatoprost (WMD = -11.88, 95%CI: -21.03 to -2.73, P = 0.01). The WMD across groups in >6 months of PGA use was -11.37 (95%CI: -17.17 to -5.58, P = 0.0001), and in <6 months of PGAs group was -8.35 (95% CI: -12.01 to -4.69, P < 0.00001), suggesting a longitudinal effect of PGAs on CCT. In conclusion, Bimatoprost and Travoprost caused a statistically significant reduction in the thickness of central cornea. Though only a few studies were included, the narrow confidence intervals and adequate sample size suggest that these findings are valid.
Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Glaucoma; Glaucoma, Open-Angle; Humans; Prostaglandins A; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Travoprost
PubMed: 35502015
DOI: 10.4103/ijo.IJO_1971_21 -
Journal of the American College of... Sep 1998Prostaglandin has been reported to have protective effects against liver injury. Use of this agent in clinical settings, however, is limited because of drug-related side...
BACKGROUND
Prostaglandin has been reported to have protective effects against liver injury. Use of this agent in clinical settings, however, is limited because of drug-related side effects. This study investigated whether misoprostol, prostaglandin E1 analogue, and OP-41483, prostaglandin I2 analogue, which have fewer adverse effects with a longer half-life, attenuate ischemic liver damage.
STUDY DESIGN
Thirty beagle dogs underwent 2 hours of hepatic vascular exclusion using venovenous bypass. Misoprostol was administered intravenously for 30 minutes before ischemia and for 3 hours after reperfusion. OP-41483 was administered intraportally for 30 minutes before ischemia (2 microg/kg/min) and for 3 hours after reperfusion (0.5 microg/kg/min). Animals were divided into five groups: untreated control group (n=10); high-dose misoprostol (total 100 microg/kg) group (MP-H, n=5); middle-dose misoprostol (50 microg/kg) group (MP-M, n=5); low-dose misoprostol (25 microg/kg) group (MP-L, n=5); and OP-41483 group (OP, n=5). Animal survival, hepatic tissue blood flow (HTBF), liver function, and histology were analyzed.
RESULTS
Two-week animal survival rates were 30% in control, 60% in MP-H, 100% in MP-M, 80% in MP-L, and 100% in OP. The treatments with prostaglandin analogues improved HTBF, and attenuated liver enzyme release, adenine nucleotrides degradation, and histologic abnormalities. In contrast to the MP-H animals that exhibited unstable cardiovascular systems, the MP-M, MP-L, and OP animals experienced only transient hypotension.
CONCLUSIONS
These results indicate that misoprostol and OP-41483 prevent ischemic liver damage, although careful dose adjustment of misoprostol is required to obtain the best protection with minimal side effects.
Topics: Analysis of Variance; Animals; Dogs; Dose-Response Relationship, Drug; Epoprostenol; Female; Ischemia; Liver; Liver Function Tests; Misoprostol; Platelet Aggregation Inhibitors; Prostaglandins, Synthetic; Reperfusion Injury
PubMed: 9740185
DOI: 10.1016/s1072-7515(98)00179-3 -
European Journal of Ophthalmology 2012
Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Humans; Intraocular Pressure; Latanoprost; Prostaglandins F, Synthetic; Timolol; Travoprost
PubMed: 22167537
DOI: 10.5301/ejo.5000077 -
Chemical Reviews Oct 2011
Review
Topics: Humans; Prostaglandin-Endoperoxide Synthases; Prostaglandins
PubMed: 21942677
DOI: 10.1021/cr2002992