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British Journal of Pharmacology May 19941. Using a range of natural and synthetic prostanoid receptor agonists and antagonists, we have shown that the rat isolated trachea contains a heterogeneous population...
1. Using a range of natural and synthetic prostanoid receptor agonists and antagonists, we have shown that the rat isolated trachea contains a heterogeneous population of prostaglandin receptor sub-types mediating both relaxation and contraction of the smooth muscle. Prostaglandin E2 (PGE2) elicits smooth muscle relaxation of pre-contracted preparations, the responses being well defined, with a mean potency (p[A50]) of 7.81 +/- 0.05. 2. 11-deoxy PGE1 16,16-dimethyl PGE2 and misoprostol were all full agonists at this receptor, whilst AH13205 was a low potency agonist, and sulprostone was inactive. 3. The EP1 receptor antagonist, AH6809 (5 microM), and the selective DP receptor antagonist, BW A868C (0.1 microM), had no significant effect on the concentration-effect (E/[A]) curves to PGE2. 4. The putative EP4-receptor antagonist, AH23848B, produced non-competitive antagonism of the PGE2 response curves; pA2 values of 5.07 +/- 0.15 and 5.24 +/- 0.19 were obtained at concentrations of 30 microM and 100 microM respectively. 5. The synthetic thromboxane A2 mimetic, U46619, caused smooth muscle contractions, with a mean p[A50] of 6.90 +/- 0.11. This response was antagonized by the TP receptor antagonist, GR32191B, yielding a mean pA2 of 8.31. 6. At concentrations of 1 microM and above, prostaglandin D2 (PGD2) and the IP-receptor agonist, cicaprost, generally elicited concentration-dependent relaxations of the rat trachea. Prostaglandin F2 alpha (PGF2 alpha) was without affinity or efficacy. 7. These data suggest that the rat isolated trachea contains EP-receptors, TP-receptors, and few, if any DP, IP or FP-receptors. The inactivity of sulprostone (EP3/EPj receptor selective) and the low potency of AH1 3205 (EP2-receptor selective) suggest that the rat trachea contains an atypical EP-receptor that does not conform to the current classification system.
Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Biphenyl Compounds; Dinoprostone; Heptanoic Acids; In Vitro Techniques; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth; Prostaglandin Endoperoxides, Synthetic; Prostaglandins E, Synthetic; Prostanoic Acids; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin E; Thromboxane A2; Trachea
PubMed: 8032634
DOI: 10.1111/j.1476-5381.1994.tb13042.x -
British Journal of Pharmacology Aug 19711. Three prostaglandin antagonists have been examined for their ability to block PGE(2) and PGF(2alpha) on human, guinea-pig and isolated rat gastrointestinal muscle.2....
1. Three prostaglandin antagonists have been examined for their ability to block PGE(2) and PGF(2alpha) on human, guinea-pig and isolated rat gastrointestinal muscle.2. 7-oxa-13-Prostynoic acid was either a non-selective antagonist, or was ineffective on the tissues studied; it had marked spasmogenic activity on the rat fundus.3. 1-Acetyl-2-(8-chloro-10,11-dihydrodibenz (b,f)(1,4) oxazepine-10-carbonyl) hydrazine selectively antagonized the excitatory effects of PGE(2) and PGF(2alpha) in guinea-pig and rat tissues, but not in human muscle.4. Polyphloretin phosphate selectively antagonized the excitatory effects of prostaglandins in both human and guinea-pig muscle preparations, but it caused stimulation of the rat fundus.5. All the antagonists lowered the tone in many tissues. They also reduced contractions caused by potassium.6. None of the compounds blocked the inhibitory effect of PGE(2) on intestinal circular muscle.7. The implication of these results on the nature of prostaglandin receptors, and the value of each compound as a prostaglandin antagonist are discussed.
Topics: Acetates; Animals; Cyclopentanes; Dibenzoxazepines; Digestive System; Fatty Acids; Guinea Pigs; Humans; Hydrazines; In Vitro Techniques; Kymography; Muscle Contraction; Muscle, Smooth; Phloretin; Potassium; Prostaglandin Antagonists; Rats; Stomach
PubMed: 5000553
DOI: 10.1111/j.1476-5381.1971.tb07142.x -
Arquivos Brasileiros de Oftalmologia Jun 2018To evaluate the efficacy of prostaglandin antagonists on blood-retinal barrier breakdown induced by anterior segment intraocular simulated surgery.
PURPOSE
To evaluate the efficacy of prostaglandin antagonists on blood-retinal barrier breakdown induced by anterior segment intraocular simulated surgery.
METHODS
Rats were randomly assigned to a negative control group, model group, nonsteroidal anti-inflammatory drugs prophylactic treatment group, nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, and corticosteroid treatment group. Four hours and 48h after modeling, the concentrations of PGE1, PGE2, and PGF2 α in the aqueous humor and vitreous body of the rat model were visualized using ELISA. The integrity of the blood-retinal barrier was quantitatively measured using Evan's blue as a tracer.
RESULTS
Four hours after modeling, the concentrations of PGE1, PGE2, and PGF2α in the aqueous humor and vitreous body in the negative control group and the nonsteroidal anti-inflammatory drugs prophylactic treatment group were significantly lower than those in the model group. The concentrations of PGE1, PGE2, and PGF2α in the aqueous humor and vitreous body in the corticosteroid prophylactic treatment group were higher than those in the negative control group and the nonsteroidal anti-inflammatory drugs prophylactic treatment group. Forty-eight hours after modeling, the concentrations of PGE1, PGE2, and PGF2α in the aqueous humor and vitreous body in the nonsteroidal anti-inflammatory drugs prophylactic treatment group, nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, and corticosteroid treatment group were lower than those in the model group, but higher than those in the negative group. Retinal Evan's blue leakage in the nonsteroidal anti-inflammatory drugs prophylactic treatment group was higher than that in the negative control group, and lower than those in the nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, corticosteroid treatment group, and model group. Retinal Evan's blue leakage in the nonsteroidal anti-inflammatory drugs treatment group, corticosteroid prophylactic treatment group, and corticosteroid treatment group were lower than those in the model group.
CONCLUSIONS
This study confirms that prostaglandin antagonists can relieve blood-retinal barrier breakdown in a rat model and that nonsteroidal anti-inflammatory drugs prophylactic treatment can achieve better efficacy.
Topics: Animals; Anterior Eye Segment; Anti-Inflammatory Agents, Non-Steroidal; Aqueous Humor; Blood-Retinal Barrier; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Humans; Male; Models, Animal; Prostaglandin Antagonists; Rats; Rats, Sprague-Dawley; Time Factors
PubMed: 29924190
DOI: 10.5935/0004-2749.20180040 -
British Medical Journal (Clinical... Sep 1983
Topics: Female; Hemostasis; Humans; Mefenamic Acid; Menstruation Disturbances; Prostaglandin Antagonists; Prostaglandins; Uterus; Vasodilation
PubMed: 6412789
DOI: 10.1136/bmj.287.6394.703 -
British Journal of Pharmacology May 2002We have characterized the prostanoid receptors involved in the regulation of human penile arterial and trabecular smooth muscle tone. Arachidonic acid induced relaxation...
We have characterized the prostanoid receptors involved in the regulation of human penile arterial and trabecular smooth muscle tone. Arachidonic acid induced relaxation of human corpus cavernosum strips (HCCS) that was blocked by the cyclo-oxygenase inhibitor, indomethacin, and augmented by the thromboxane receptor (TP) antagonist, SQ29548, suggesting that endogenous production of prostanoids regulates penile smooth muscle tone. TP-receptors mediate contraction of HCCS and penile resistance arteries (HPRA), since the agonist of these receptors, U46619, potently contracted HCCS (EC50 8.3+/-2.8 nM) and HPRA (EC50 6.2+/-2.2 nM), and the contractions produced by prostaglandin F(2alpha) at high concentrations (EC50 6460+/-3220 nM in HCCS and 8900+/-6700 nM in HPRA) were inhibited by the selective TP-receptor antagonist, SQ29548 (0.02 microM). EP-receptors are responsible for prostanoid-induced relaxant effects in HCCS because only prostaglandin E1 (PGE1), prostaglandin E2 and the EP2/EP4-receptor agonist, butaprost, produced consistent relaxation of this tissue (EC50 93.8+/-31.5, 16.3+/-3.8 and 1820+/-1284 nM, respectively). In HPRA, both prostacyclin and PGE1 (EC50 60.1+/-18.4 and 109.0+/-30.9 nM, respectively) as well as the selective IP receptor agonist, cicaprost, and butaprost (EC50 25.2+/-15.2 and 7050+/-6020 nM, respectively) caused relaxation, suggesting co-existence of IP- and EP-receptors (EP2 and/or EP4). In summary, endogenous production of prostanoids may regulate penile smooth muscle contractility by way of specific receptors. TP-receptors mediate contraction in HCCS and HPRA, while the relaxant effects of prostanoids are mediated by EP2- and/or EP4-receptors in HCCS and by EP- and IP-receptors in HPRA.
Topics: Alprostadil; Arachidonic Acid; Arteries; Cyclic AMP; Dinoprost; Humans; In Vitro Techniques; Male; Muscle Contraction; Muscle Relaxation; Muscle Tonus; Muscle, Smooth; Muscle, Smooth, Vascular; Penis; Prostaglandins; Receptors, Prostaglandin; Vascular Resistance
PubMed: 11976264
DOI: 10.1038/sj.bjp.0704675 -
Ultrasound in Obstetrics & Gynecology :... Sep 2021To test the hypotheses that estimated mean pulmonary arterial pressure (MPAP) decreases and pulmonary vascular maturation, assessed by the ratio of pulmonary arterial...
OBJECTIVES
To test the hypotheses that estimated mean pulmonary arterial pressure (MPAP) decreases and pulmonary vascular maturation, assessed by the ratio of pulmonary arterial flow acceleration time to ejection time (AT/ET ratio), increases after reversal of fetal ductus arteriosus constriction by reducing maternal intake of the causal agent (prostaglandin inhibitors, such as polyphenol-rich foods or non-steroidal anti-inflammatory drugs), and that these effects are independent of gestational age, which are inferences not yet demonstrated in the clinical setting.
METHODS
This was a prospective cohort study comparing Doppler echocardiographic ductal flow dynamics, MPAP and pulmonary arterial flow AT/ET ratio in third-trimester fetuses (≥ 28 weeks' gestation) with ductus arteriosus constriction, at the time of diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors either by suspending the use of pharmacological agents with potential for prostaglandin inhibition or by restricting the consumption of polyphenol-rich foods. MPAP was estimated using the Dabestani equation (MPAP = 90 - (0.62 × AT)), and pulmonary vascular maturity was assessed using the AT/ET ratio, according to reported validation studies. Student's t-test was used for comparison of variables at diagnosis with those after reversal of ductal constriction. Change in MPAP and pulmonary AT/ET ratio between the two assessments was compared with the expected change in the same gestational period in normal fetuses based on reference curves of MPAP and pulmonary AT/ET ratio constructed in normal fetuses from healthy pregnant women at 19-37 weeks' gestation, encompassing the same gestational age range as the study group (28-37 weeks).
RESULTS
Seventy pregnancies with fetal ductus arteriosus constriction were included in the study. After 2 weeks of reduced maternal intake of prostaglandin inhibitors, normalization of mean systolic (change from 1.86 ± 0.34 m/s at diagnosis to 1.38 ± 0.41 m/s; P < 0.001) and diastolic (change from 0.41 ± 0.11 m/s to 0.21 ± 0.065 m/s; P < 0.001) ductal velocities and of mean pulsatility index (change from 1.99 ± 0.20 to 2.55 ± 0.42; P < 0.001) was demonstrated. MPAP decreased between the assessments (change from 66.7 ± 6.90 mmHg at diagnosis to 54.5 ± 6.70 mmHg after 2 weeks; P < 0.001) and mean pulmonary AT/ET ratio increased (change from 0.20 ± 0.06 to 0.33 ± 0.07; P < 0.001). Change in MPAP between diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors was -12.2 ± 0.30 mmHg, which was 5.3-times higher than that in 305 normal fetuses over 2 weeks during the same gestational period (-2.3 ± 0.19 mmHg) (P < 0.001), and change in pulmonary AT/ET ratio between the two assessments was 0.13 ± 0.08, which was 8.7-times higher than that in normal fetuses in the same gestational period (0.015 ± 0.08) (P < 0.001).
CONCLUSIONS
Resolution of fetal ductal constriction is followed by a fall in MPAP and by an increase in pulmonary vascular maturity, to a significantly greater degree than is observed in normal fetuses in the same gestational-age period. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Adult; Arterial Pressure; Blood Flow Velocity; Constriction, Pathologic; Ductus Arteriosus; Echocardiography, Doppler; Female; Fetal Development; Fetus; Gestational Age; Humans; Hypertension, Pulmonary; Polyphenols; Pregnancy; Prenatal Care; Prospective Studies; Prostaglandin Antagonists; Pulmonary Artery; Pulsatile Flow; Stroke Volume; Ultrasonography, Prenatal
PubMed: 33502049
DOI: 10.1002/uog.23599 -
Gut Dec 1986Because endogenous prostaglandins may protect the gastric mucosa a study was conducted to determine factors influencing the synthesis of immunoreactive prostaglandin...
Because endogenous prostaglandins may protect the gastric mucosa a study was conducted to determine factors influencing the synthesis of immunoreactive prostaglandin (iPG) E2 and thromboxane (iTx) B2 as measured by radioimmunoassay and prostaglandin catabolism measured radiometrically, in human gastric mucosa. Gastric mucosa was obtained at endoscopy. Synthesis of iPE2 and iTxB2 was inhibited in vitro by indomethacin; iTxB2 synthesis was also selectively inhibited by the thromboxane synthesis inhibitor dazmegrel. Prostaglandin catabolism was inhibited by carbenoxolone. Multivariate analysis showed that synthesis of iPGE2 from endogenous precursor during homogenisation was decreased in patients on non-steroidal anti-inflammatory drugs. Mucosal inflammation was associated with significantly increased synthesis of iPGE2 and decreased prostaglandin catabolism. There were no differences between the mucosa of patients with or without gastric ulcers, nor between the ulcer rim and mucosa 5 cm away. Age, sex, smoking history and ingestion of antisecretory drugs appeared to exert no influence. In this study gastritis was the major influence on prostaglandin synthesis. It seems unlikely that prostaglandin deficiency is a strong predisposing factor for gastric ulceration.
Topics: Dinoprostone; Female; Gastric Mucosa; Gastritis; Humans; Indomethacin; Male; Prostaglandin Antagonists; Prostaglandins; Prostaglandins E; Radioimmunoassay; Stomach Ulcer; Thromboxane B2
PubMed: 3468053
DOI: 10.1136/gut.27.12.1484 -
The Angle Orthodontist Apr 2002Orthodontically induced inflammatory root resorption (OIIRR) or, as it is better known, root resorption, is an unavoidable pathologic consequence of orthodontic tooth... (Review)
Review
Orthodontically induced inflammatory root resorption (OIIRR) or, as it is better known, root resorption, is an unavoidable pathologic consequence of orthodontic tooth movement. It is a certain adverse effect of an otherwise predictable force application. Although it is rarely serious, it is a devastating event when it is radiographically recognized. Orthodontics is probably the only dental specialty that actually uses the inflammatory process as a means of solving functional and esthetic problems. Force application initiates a sequential cellular process. We know exactly how and when it is evoked, but we are unable to predict its actual overall outcome. The extent of this inflammatory process depends on many factors such as the virulence or aggressiveness of the different resorbing cells, as well as the vulnerability and sensitivity of the tissues involved. Individual variation and susceptibility, which are related to this process, remain beyond our understanding. We are therefore unable to predict the incidence and extent of OIIRR after force application. This contemporary review is divided into two parts. In Part I, we discuss the basic sciences aspects of OIIRR as a continuation of our previously published work. In Part II, we present the clinical aspects of this subject.
Topics: Animals; Cementogenesis; Dental Cementum; Dental Stress Analysis; Diphosphonates; Humans; Inflammation; Orthodontic Appliances; Orthodontics, Corrective; Osteoclasts; Prostaglandin Antagonists; Root Resorption; Thyroxine
PubMed: 11999941
DOI: 10.1043/0003-3219(2002)072<0175:OIIRRP>2.0.CO;2 -
Physiology International Mar 2016The purpose of this study was to determine the activity of the autonomic nervous system (ANS), using spectral analysis of the heart rate variability (HRV) in the model...
The purpose of this study was to determine the activity of the autonomic nervous system (ANS), using spectral analysis of the heart rate variability (HRV) in the model of partial bladder outlet obstruction (PBOO) in rats treated with selected non-steroidal anti-inflammatory drugs (NSAID): piroxicam (PRX) or meloxicam (MLX), and following administration of PGF2a prostaglandin analogue (Enzaprost F5). Neither the use of PGF2a analogue nor of MLX, caused significant changes in the HRV spectrum (except for HRV spectrum total power reduction with MLX). The use of PRX caused reduction of the total power and powers of all components of the HRV spectrum (except for VLF). Moreover, increased nLF and reduced nHF were observed. The obtained results suggest that the total prostaglandin synthesis block with a non-selective cyclooxygenase inhibitor (PRX) results in reduced ANS total activity, with decreased parasympathetic activity and a relative sympathetic predominance. The preferential cyclooxygenase-2 block (MLX) caused reduction of the total ANS activity as well, however with no clear disproportion of any part of the ANS. Therefore, prostaglandin synthesis inhibition and associated decrease of parasympathetic activity may constitute an additional and favourable feature of NSAID pharmacodynamics in the treatment of BPH.
Topics: Animals; Cyclooxygenase 2 Inhibitors; Dinoprost; Disease Models, Animal; Heart Rate; Meloxicam; Molecular Targeted Therapy; Piroxicam; Prostaglandin Antagonists; Prostaglandins; Prostaglandins, Synthetic; Rats; Rats, Wistar; Thiazines; Thiazoles; Urinary Bladder Neck Obstruction; Urodynamics
PubMed: 27030625
DOI: 10.1556/036.103.2016.1.3 -
European Journal of Pharmacology Jul 2019Acute lung injury (ALI) and acute respiratory distress syndrome are life-threatening conditions that still have no definite pharmacotherapy. Hence, we investigate the...
Acute lung injury (ALI) and acute respiratory distress syndrome are life-threatening conditions that still have no definite pharmacotherapy. Hence, we investigate the potential effectiveness and underlying mechanism of CT-133, a newly developed selective antagonist of prostaglandin D2 receptor 2 (DP2) or of chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2), against lipopolysaccharide (LPS)-induced ALI. CT-133 (10 or 30 mg/kg) or dexamethasone (1 mg/kg, positive control) were intragastrically administered 1 h before and 12 h after intratracheal LPS instillation, and primary neutrophils and macrophages and RAW264.7 macrophages were used to investigate the role of CT-133 in regulation of their functions. LPS induced a significant secretion of PGD from primary macrophages, however, CT-133 dose-dependently and markedly decreased the infiltration of neutrophils and macrophages into lungs, reduced the IL-1β, TNF-α, IL-6, and KC levels in broncho-alveolar lavage (BAL) fluids, decreased the wet weight and myeloperoxidase activity of lungs, reduced Evans blue and albumin exudation into lungs, and improved the lung histopathological changes and hypoxemia. Moreover, CT-133 significantly suppressed the primary neutrophil migration toward the PGD and robustly inhibited the mRNA and protein expression of IL-1β, TNF-α, IL-6, and KC in primary and RAW264.7 macrophages in response to either LPS- or PGD stimulation. Finally, CT-133 significantly blocked the LPS-induced P65 activation in both RAW264.7 macrophages and mouse lungs. Thus, This is the first report that a CRTH2 antagonist, CT-133, is capable of significantly alleviating LPS-induced lung injury by probably down-regulating the NF-κB signalling.
Topics: Acute Lung Injury; Animals; Boronic Acids; Bronchoalveolar Lavage Fluid; Cell Movement; Chemokines; Lipopolysaccharides; Lung; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; NF-kappa B; Neutrophils; Permeability; Prostaglandin D2; RAW 264.7 Cells; Receptors, Immunologic; Receptors, Prostaglandin; Signal Transduction
PubMed: 30951719
DOI: 10.1016/j.ejphar.2019.03.053