Meclofenamate inhibits prostaglandin E binding and adenylyl cyclase activation in human myometrium

Bernal, Andrés López; Buckley, Sue; Rees, C. M. P.; Marshall, J. F.

doi:10.1677/joe.0.1290439

Cited by 21 publications

(4 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relationship between heavy menstruation and pain as an inflammatory response caused by increased prostaglandin synthesis is well established. The serum levels of prostaglandins, specifically prostaglandin E2 [21] or F2a [22], are higher in women with heavy menstrual bleeding (HMB) as shown by data compiled over 30 years. Nonsteroidal anti-inflammatory drugs (NSAIDs) help reduce HMB by inhibiting cyclo-oxygenase, thereby reducing prostaglandin production [2123].…”

Section: Discussionmentioning

confidence: 99%

Polycystic ovarian morphology is associated with primary dysmenorrhea in young Korean women

et al. 2019

View full text Add to dashboard Cite

ObjectiveThis study was aimed at identifying a correlation between polycystic ovarian morphology (PCOM) and the severity of primary dysmenorrhea in young Korean women.MethodsA total of 592 patients who visited a tertiary hospital from March 2008 to March 2015 for dysmenorrhea were examined. After excluding those with secondary causes of menstrual pain (for example, myoma, adenomyosis, endometriosis, and pelvic inflammatory disease), 361 women were recruited and retrospectively analyzed. Severe dysmenorrhea was defined as a visual analog scale (VAS) score ≥6.ResultsThe mean patient age was 23.0±4.0 years, the average menstrual cycle length was 34.4±23.7 days, and the average pain intensity was VAS 6.7±0.1 at baseline. PCOM was assessed by ultrasound in 54 women (15%). Patients with severe menstrual pain were more likely to have irregular menstrual cycles (P=0.03) and heavy menstrual flow (P=0.01) than those with mild menstrual pain. After adjusting for weight, height, menstrual cycle interval, and menstrual flow in the logistic regression analysis, PCOM (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.05–4.97; P=0.04) and heavy menstrual flow (OR, 1.85; 95% CI, 1.05–3.28; P=0.04) were found to be significant independent factors influencing pain.ConclusionOur study shows that PCOM may have a correlation with the severity of primary dysmenorrhea. Since PCOM may play a role in the development of menstrual pain, patients with PCOM should be under active surveillance with resources for prompt pain management readily available. It may also be necessary to further investigate the molecular mechanisms of pain development in primary dysmenorrhea.

show abstract

Section: Discussionmentioning

confidence: 99%

Polycystic ovarian morphology is associated with primary dysmenorrhea in young Korean women

et al. 2019

View full text Add to dashboard Cite

show abstract

“…cAMP was measured by the competitive protein-binding assay of Brown et al (1971) as described by López Bernal et al (1991) using [ 3 H]cAMP as tracer. All compounds were dissolved initially in ethanol or dimethylsulphoxide (DMSO), and solvent controls were included in the experiments.…”

Section: Measurement Of Intracellular Campmentioning

confidence: 99%

Characterization of adenylyl cyclases in cultured human granulosa cells

Asbóth¹,

Price²,

Bellinger³

et al. 2001

Reproduction

View full text Add to dashboard Cite

Granulosa cells play an essential role in follicular development and formation of corpora lutea. Many functions of granulosa-lutein cells are controlled by activation of G protein-coupled receptors and the formation of cyclic AMP (cAMP) by adenylyl cyclase. There are at least nine mammalian adenylyl cyclase isoenzymes, which show different sensitivities towards other signalling systems. The aim of this study was to identify the types of adenylyl cyclase present in human granulosa cells and to investigate its functional regulation by G proteins, calcium and the protein kinase C and A pathways. Granulosa cells were obtained from women undergoing IVF. The cells were maintained in primary culture and they consistently expressed mRNA coding for adenylyl cyclase I, III, VI, VII and IX. The signals for adenylyl cyclase V and VIII were more variable among patients and there was no signal for adenylyl cyclase II. The expression of multiple adenylyl cyclase proteins was confirmed by immunochemistry with subtype-specific antibodies. The formation of cAMP in cultured cells was stimulated many times by hCG (EC(50) value 4.2 iu ml(-1)) and by prostaglandin E(2) (PGE(2); EC(50) = 0.75 micromol l(-1)) in a concentration-dependent manner, thus confirming the presence of receptors coupled positively to G(s). The diterpene forskolin, which stimulates all isoforms of adenylyl cyclase except for adenylyl cyclase IX, increased cAMP formation to higher levels than hCG or PGE(2). The strong stimulation by forskolin indicates that adenylyl cyclase IX is unlikely to be the major source of cyclase activity in these cells. Basal and forskolin- or PGE(2)-stimulated adenylyl cyclase activity was amplified 1.5-2.0 times by phorbol-12,13-dibutyrate, indicating that protein kinase C-sensitive enzymes (for example, adenylyl cyclase types IV, V, VI or VII) may be active in the cells. In contrast, hCG-stimulated activity was inhibited (76 +/- 6%) by phorbol ester. Stimulation of G(i) with the alpha-adrenoceptor agonist clonidine inhibited hCG-induced cyclase activity. This finding indicates that adenylyl cyclase II and IV subtypes, which are stimulated by betagamma subunits released from G(i), are not predominant. Increases in intracellular free calcium concentrations by the ionophore A23187, the calcium-ATPase inhibitor thapsigargin or by fluprostenol, a selective prostanoid FP receptor agonist, which is known to open calcium channels in granulosa cells, or removal of calcium by EGTA, had no significant effects on basal or forskolin-stimulated formation of cAMP. These results indicate that subtypes adenylyl cyclase I, III and VIII, which are activated by calcium, and adenylyl cyclase V and VI, which are inhibited by calcium, are not dominant isoforms in granulosa-lutein cells. The protein kinase A inhibitor H89 had no effects on formation of cAMP; this finding rules out the involvement of adenylyl cyclase V and VI subtypes, which are subjected to negative feedback by protein kinase A. These results indicate that adenylyl cyclase VII is the dominan...

show abstract

“…The EC50 value is defined as the agonist concentration that produces 50% of the maximal response.Protein was assayed by the method of Bradford(1976). cAMP formation was measured as described previously(López Bernal et al 1991) using a competi¬ tive protein-binding assay(Brown et al 1972). Low Philadelphia, PA, U.S.A.).…”

mentioning

confidence: 99%

Oxytocin-stimulated phosphoinositide hydrolysis in human myometrial cells: involvement of pertussis toxin-sensitive and -insensitive G-proteins

Phaneuf

Europe‐Finner²,

Varney³

et al. 1993

Journal of Endocrinology

147

View full text Add to dashboard Cite

Phosphoinositide hydrolysis is important in mediating the actions of oxytocin and prostaglandin (PG) F2 alpha on uterine contractions during labour. We have measured the effect of oxytocin, PGF2 alpha and other agents on the formation of inositol phosphates (IPs) in cultured human myometrial cells labelled with [3H]inositol and on changes in intracellular free Ca2+ concentration ([Ca2+]i) in cells loaded with Fura-2. Oxytocin induced the formation of [3H]IPs in a concentration-dependent manner with an EC50 (concentration of agonist producing 50% of the maximal response) of 1.4 +/- 0.5 nmol/l (mean +/- S.E.M.). The maximal response was obtained with 1 mumol oxytocin/l and represented a stimulation of 670% over basal. PGF2 alpha also stimulated the formation of [3H]IPs and the response at 1 mumol/l was a 204% stimulation over basal. The effects of PGF2 alpha were independent of extracellular Ca2+ but the effect of oxytocin was reduced with low extracellular Ca2+. Cyclic AMP formation, induced by forskolin or PGE2, had no effect on the stimulated levels of [3H]IPs. Pertussis toxin (PT) reduced the oxytocin-stimulated formation of [3H]IPs in a concentration-dependent manner. The maximal effect of PT resulted in an 80% reduction in the formation of [3H]IPs. However, PGF2 alpha stimulation was not affected by PT treatment. To analyse the action of PT further, we studied its effect on oxytocin-induced changes in [Ca2+]i. The basal [Ca2+]i was 112 +/- 4 nmol/l (n = 225 cells) and was not affected by PT treatment (109 +/- 3 nmol/l; n = 200 cells). In the absence of PT, 1 mumol oxytocin/l increased [Ca2+]i to a peak of 522 +/- 26 nmol/l, and in PT-treated cells, the [Ca2+]i peak was reduced to 348 +/- 16 nmol/l. Similar inhibitory effects of PT were obtained at oxytocin concentrations ranging from 1 to 100 nmol/l. Our data suggest that in human myometrial cells, the oxytocin-induced production of [3H]IPs and increase in [Ca2+]i are mediated by a PT-sensitive G-protein. However, a significant fraction of the oxytocin response appears to be mediated by a PT-insensitive G-protein, possibly a member of the Gq family.

show abstract

Meclofenamate inhibits prostaglandin E binding and adenylyl cyclase activation in human myometrium

Cited by 21 publications

References 13 publications

Polycystic ovarian morphology is associated with primary dysmenorrhea in young Korean women

Polycystic ovarian morphology is associated with primary dysmenorrhea in young Korean women

Characterization of adenylyl cyclases in cultured human granulosa cells

Oxytocin-stimulated phosphoinositide hydrolysis in human myometrial cells: involvement of pertussis toxin-sensitive and -insensitive G-proteins

Contact Info

Product

Resources

About