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Proceedings of the National Academy of... Mar 1998Zona pellucida protein 3, a protein of the egg's extracellular matrix, and progesterone secreted by granulosa cells surrounding the oocyte are regarded as physiological...
Zona pellucida protein 3, a protein of the egg's extracellular matrix, and progesterone secreted by granulosa cells surrounding the oocyte are regarded as physiological stimuli of sperm acrosome reaction. Signal transduction steps initiated by both stimuli result in influx of Ca2+ from the extracellular space. Herein, we propose a role for prostaglandin (PG) E as a physiological inducer of Ca2+ influx and acrosome reaction in human spermatozoa. PGE1 specifically binds to human sperm membranes (Kd = 20.4 nM; Bmax = 88 fmol/mg protein) and induces a pertussis toxin-insensitive, transient increase in intracellular Ca2+ concentrations, which can be blocked by microM concentrations of La3+, Gd3+, and Zn2+. The kinetic profile was similar to that observed after progesterone challenge. Sequential application of both agonists did not lead to cross-desensitization. E prostaglandins were found to be the only prostanoids with agonistic properties (EC50 values for PGE1 and PGE2: <10 nM and 300 nM, respectively). Pharmacological characteristics were not compatible with those of cloned prostanoid receptors indicating the expression of a distinct membrane receptor. Activation of the sperm E prostanoid receptor stimulates incorporation of [alpha-32P]GTP azidoanilide into immunoprecipitated Galphaq/11 subunits. Thus, in human sperm, PG induces Ca2+ influx and acrosome reaction via a Gq/11-coupled E prostanoid receptor. The block of PGE1-induced Ca2+ transients and acrosome reaction by physiological Zn2+ concentrations highlights a role of Zn2+ as an endogenous Ca2+ channel blocker present in seminal plasma protecting sperm from premature PGE1-evoked increases in intracellular Ca2+ concentrations.
Topics: Acrosome; Alprostadil; Calcium; Calcium Channel Blockers; Cyclic AMP; Dinoprostone; GTP-Binding Proteins; Humans; Male; Prostaglandins E; Receptors, Prostaglandin E; Signal Transduction; Spermatozoa; Zinc
PubMed: 9501206
DOI: 10.1073/pnas.95.6.3008 -
British Medical Journal (Clinical... May 1984Concentrations of prostaglandins E, F, and 6-keto-prostaglandin F1 alpha were estimated in central venous blood and amniotic fluid in 21 women with eclampsia and 16...
Concentrations of prostaglandins E, F, and 6-keto-prostaglandin F1 alpha were estimated in central venous blood and amniotic fluid in 21 women with eclampsia and 16 healthy pregnant controls. Central venous blood concentrations of 6-keto-prostaglandin F1 alpha and prostaglandin E were significantly lower in patients than controls before delivery and remained reduced for at least 48 hours after delivery. Low concentrations of prostaglandins E and 6-keto-prostaglandin F1 alpha are probably directly related to the pathogenesis of eclampsia.
Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Amniotic Fluid; Eclampsia; Female; Humans; Pregnancy; Prostaglandins E; Prostaglandins F
PubMed: 6426613
DOI: 10.1136/bmj.288.6429.1487 -
Gut Sep 1983The effects of non-steroidal anti-inflammatory drugs and prostaglandins E(2) and F(2alpha) on the secretory and electrical activity of isolated rabbit fundic mucosa have...
The effects of non-steroidal anti-inflammatory drugs and prostaglandins E(2) and F(2alpha) on the secretory and electrical activity of isolated rabbit fundic mucosa have been studied. Spontaneous acid secretion was inhibited by serosal side application of sodium thiocyanate (6x10(-2)M) and the resulting alkali secretion measured by pH stat tiration. Serosal side application of indomethacin (10(-5)M) or aspirin (3x10(-3)M) inhibited alkali secretion (0.55+/-0.06 to 0.12+/-0.06 mumol/cm(2)/h, n=6, p<0.01 and 0.28+/-0.06 to 0.11+/-0.03 mumol/cm(2)/h, n=7, p<0.02 respectively). Mucosal or serosal side prostaglandin E(2) (10(-5) to 10(-10)M) and F(2alpha) (10(-4) to 10(-10)M) failed to alter the rate of alkalinisation but secretion was significantly increased by serosal side 16,16-dimethyl-prostaglandin E(2) (10(-6)M) (0.90+/-0.20 to 1.50+/-0.30 mumol/cm(2)/h, n=6, p<0.01). Serosal side application of 10(-6)M prostaglandin E(2) to fundic mucosae pretreated with either aspirin (5x10(-3)M) or indomethacin (10(-5)M), to reduce endogenous E(2) formation, also failed to alter alkali secretion. Pretreatment of the mucosa with 16,16-dimethyl-E(2) (10(-6)M) abolished the inhibitory effect of indomethacin (10(-5)M) on alkali secretion (n=6) but did not modify the secretory response to aspirin (3x10(-3)M) (fall in alkali secretion with aspirin = 81+/-11% and with aspirin plus 16,16-dimethyl-E(2) = 72+/-10%, n=7). In the doses used, none of the prostaglandins or non-steroidal anti-inflammatory drugs altered transmucosal potential difference or electrical resistance. These results show that the damaging agents, aspirin and indomethacin, both inhibit gastric alkali secretion but that modes of action may differ. The observation that prostaglandins, E(2) and F(2alpha) failed to increase alkali production suggests that their protective activity against a variety of damaging agents as shown by others, may be mediated by another mechanism.
Topics: Alkalies; Animals; Anti-Inflammatory Agents; Aspirin; Dinoprost; Dinoprostone; Gastric Fundus; In Vitro Techniques; Indomethacin; Mucous Membrane; Prostaglandins E; Prostaglandins F; Rabbits; Serous Membrane
PubMed: 6576966
DOI: 10.1136/gut.24.9.784 -
Fertility and Sterility Sep 1975The concentration of prostaglandin E (PGE) was measured in the semen of 5 men of proven fertility and in 12 men of couples who were infertile but in whom no abnormality...
The concentration of prostaglandin E (PGE) was measured in the semen of 5 men of proven fertility and in 12 men of couples who were infertile but in whom no abnormality had been detected by conventional semen analysis, postcoital test of sperm motility, endometrial biopsy, and laparoscopic dye insufflation of the fallopian tubes. In the fertile men the mean PGE concentration was 52.7 +/- 9.9 mug/ml, and in infertile men the concentration was 22.1 +/- 2.76 mug/ml; the difference between the two groups was highly significant (P less than 0.001). In five of the infertile men attempts were made to raise the PGE concentration by the administration of either corn oil, which contains the prostaglandin precursor linoleic acid, or caffeine, which inhibits prostaglandin degradation; the response to both agents was insignificant.
Topics: Caffeine; Female; Humans; Infertility, Male; Male; Oils; Prostaglandins E; Semen; Zea mays
PubMed: 1183642
DOI: 10.1016/s0015-0282(16)41349-x -
Fertility and Sterility Nov 1978
Topics: Adult; Fallopian Tubes; Female; Humans; Muscle Contraction; Muscle, Smooth; Prostaglandins E; Prostaglandins F
PubMed: 720643
DOI: 10.1016/s0015-0282(16)43637-x -
The Journal of Biological Chemistry Mar 2022Toll-like receptors (TLRs) are pattern recognition receptors that play a critical role in innate immune diseases. TLR3, which is localized in the endosomal compartments...
Toll-like receptors (TLRs) are pattern recognition receptors that play a critical role in innate immune diseases. TLR3, which is localized in the endosomal compartments of hematopoietic immune cells, is able to recognize double-stranded RNA (dsRNA) derived from viruses and bacteria and thereby induce innate immune responses. Inflammatory periodontal bone resorption is caused by bacterial infections, which initially is regulated by innate immunity; however, the roles of TLR3 signaling in bone resorption are still not known. We examined the roles of TLR3 signaling in bone resorption using poly(I:C), a synthetic dsRNA analog. In cocultures of mouse bone marrow cells and stromal osteoblasts, poly(I:C) clearly induced osteoclast differentiation. In osteoblasts, poly(I:C) increased PGE production and upregulated the mRNA expression of PGE-related genes, Ptgs2 and Ptges, as well as that of a gene related to osteoclast differentiation, Tnfsf11. In addition, we found that indomethacin (a COX-2 inhibitor) or an antagonist of the PGE receptor EP4 attenuated the poly(I:C)-induced PGE production and subsequent Tnfsf11 expression. Poly(I:C) also prolonged the survival of the mature osteoclasts associated with the increased mRNA expression of osteoclast marker genes, Nfatc1 and Ctsk. In ex vivo organ cultures of periodontal alveolar bone, poly(I:C) induced bone-resorbing activity in a dose-dependent manner, which was attenuated by the simultaneous administration of either indomethacin or an EP4 antagonist. These data suggest that TLR3 signaling in osteoblasts controls PGE production and induces the subsequent differentiation and survival of mature osteoclasts. Endogenous TLR3 in stromal osteoblasts and osteoclasts synergistically induces inflammatory alveolar bone resorption in periodontitis.
Topics: Animals; Bone Resorption; Cells, Cultured; Dinoprostone; Endosomes; Indomethacin; Mice; Osteoblasts; Osteoclasts; Prostaglandins E; RANK Ligand; RNA, Messenger; Toll-Like Receptor 3
PubMed: 35101442
DOI: 10.1016/j.jbc.2022.101603 -
Kidney International Jun 1981
Review
Topics: Adenylyl Cyclase Inhibitors; Animals; Bufonidae; Cell Membrane Permeability; Cyclic AMP; Dogs; Humans; Kidney; Prostaglandins; Prostaglandins E; Rabbits; Rats; Stimulation, Chemical; Thromboxane A2; Thromboxane B2; Urinary Bladder; Vasopressins; Water
PubMed: 6267350
DOI: 10.1038/ki.1981.87 -
British Medical Journal Sep 1979
Topics: Female; Humans; Labor, Induced; Pessaries; Pregnancy; Prostaglandins E
PubMed: 497784
DOI: 10.1136/bmj.2.6191.671-b -
The Journal of Physiology Jul 19811. The effect of i.v. administration of prostaglandin (PG) E(2) (10-40 mug kg(-1) h(-1)), 16,16-dimethyl PGE(2) (0.1-0.5 mug kg(-1) h(-1)), PGE(1) (16-20 mug kg(-1)...
1. The effect of i.v. administration of prostaglandin (PG) E(2) (10-40 mug kg(-1) h(-1)), 16,16-dimethyl PGE(2) (0.1-0.5 mug kg(-1) h(-1)), PGE(1) (16-20 mug kg(-1) h(-1)), PGA(1) (5-11 mug kg(-1) h(-1)) and PGF(2alpha) (40 mug kg(-1) h(-1)) on the relationship between [H(+)] and flow of gastric juice during stimulation of gastric secretion by pentagastrin was investigated in conscious cats prepared with cannulated gastric fistulae.2. A- and E-type prostaglandins significantly reduced pentagastrin-stimulated acid output. This inhibition was associated with a reduction of the [H(+)] of the gastric juice such that the [H(+)] observed at any flow rate tended to be lower than the normal range observed with pentagastrin alone. With the highest doses of these prostaglandins the mean [H(+)] values were well below the normal range with pentagastrin alone.3. At the dose tested, PGF(2alpha) had little effect on acid output, and did not alter the relationship between [H(+)] and gastric flow.4. There is a linear relationship between acid output and gastric flow and this relationship is similar during stimulation of gastric secretion by pentagastrin, histamine or insulin. Gastric acid inhibitory doses of cimetidine, atropine and somatostatin did not alter this relationship. In contrast the A- and E-type prostaglandins displaced this relationship to the right of the normal line observed with the acid stimulants alone. A- and E-type prostaglandins reduced the slope of the line relating acid output and gastric flow from approximately 150-170 muequiv/ml(-1) to approximately 100-120 muequiv ml(-1), this being taken as evidence of dilution of the parietal H(+) secretion with a non-parietal secretion.5. The volume of non-parietal gastric secretion was calculated as the gastric flow at zero acid output by extrapolation of linear plots of acid output versus gastric flow. Unstimulated gastric flow measured directly was 0.75 ml 15 min(-1). The calculated non-parietal flow was in the range 0.52-0.90 ml 15 min(-1) during stimulation of gastric secretion with pentagastrin, histamine and insulin, and inhibition of pentagastrin-stimulated acid secretion with cimetidine, atropine and somatostatin. PGE(2) (1.51 ml 15 min(-1)) and 16,16-dimethyl PGE(2) (1.20 ml 15 min(-1)) nearly doubled the calculated non-parietal flow.6. These data demonstrate that gastric acid inhibitory doses of A- and E-type prostaglandins can reduce the [H(+)] in the bulk fluid of the gastric lumen during stimulation of acid secretion. The data provide evidence that these prostaglandins stimulate a non-parietal component of gastric secretion. This might be gastric bicarbonate and mucus secretion.
Topics: Alprostadil; Animals; Cats; Dinoprost; Dinoprostone; Gastric Acid; Gastric Juice; Hydrogen-Ion Concentration; Pentagastrin; Prostaglandins; Prostaglandins A; Prostaglandins E; Prostaglandins F; Secretory Rate
PubMed: 6948108
DOI: 10.1113/jphysiol.1981.sp013798 -
British Journal of Cancer Apr 1984Prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) were measured by Gas Liquid Chromatography-Mass Spectrometry (GLC-MS) in extracts of 100 human mammary carcinomas....
Prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) were measured by Gas Liquid Chromatography-Mass Spectrometry (GLC-MS) in extracts of 100 human mammary carcinomas. All tumours contained measurable amounts of both prostaglandins but wide variations between individual tumours were observed. Values for PGE2 ranged from 7 to 762 ng g-1 tissue with a median of 100 ng g-1 tissue. Values for PGF2 alpha ranged from 3 to 475 ng g-1 tissue (median 60 ng g-1 tissue). There was a highly significant positive correlation between amounts of the 2 prostaglandins in individual tumours. Amounts of both PGE2 and PGF2 alpha were not significantly related to the menopausal status of the patients or the presence of oestrogen and progesterone receptors.
Topics: Breast Neoplasms; Cell Count; Dinoprost; Dinoprostone; Female; Gas Chromatography-Mass Spectrometry; Humans; Menopause; Prostaglandins E; Prostaglandins F; Receptors, Estrogen; Receptors, Progesterone
PubMed: 6585216
DOI: 10.1038/bjc.1984.73