scholarly journals Changes in cAMP effector predominance are associated with increased oxytocin receptor expression in twin but not infection-associated or idiopathic preterm labour

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0240325
Author(s):  
Angela Yulia ◽  
Alice J. Varley ◽  
Natasha Singh ◽  
Kaiyu Lei ◽  
Rachel Tribe ◽  
...  
Keyword(s):  
Preterm Labour ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Oxytocin Receptor ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Effector Pathway ◽  
Effector System ◽  
Term Labour ◽  
Camp Levels

We previously reported that at term pregnancy, a decline in myometrial protein kinase A (PKA) activity leads to an exchange protein activated by cyclic AMP (Epac1)-dependent increase in oxytocin receptor (OTR) expression, promoting the onset of labour. Here, we studied the changes in the cyclic adenosine monophosphate (cAMP) effector system present in different phenotypes of preterm labour (PTL). Myometrial biopsies obtained from women with phenotypically distinct forms of PTL and the levels of PKA and OTR were examined. Although we found similar changes in the cAMP effector pathway in all forms of PTL, only in the case of twin PTL (T-PTL) was myometrial OTR levels increased in association with these results. Although there were several changes in the mRNA levels of components of the cAMP synthetic pathway, the total myometrial cAMP levels did not change with the onset of any subtype of PTL. With regards to the expression of cAMP-responsive genes, we found that the mRNA levels of 4 of the 5 cAMP-down-regulated genes were increased in T-PTL, similar to our findings in term labour. These data signify that although changes in the cAMP effector system were common to all forms of PTL, only in T-PTL were OTR levels increased. Similarly, the mRNA levels of cAMP-repressed genes were only increased in T-PTL supporting the concept that the decline in PKA levels influences myometrial function driving the onset of T-PTL.

scholarly journals The interaction between protein kinase A and progesterone on basal and inflammation-induced myometrial oxytocin receptor expression

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0239937
Author(s):  
Angela Yulia ◽  
Alice J. Varley ◽  
Natasha Singh ◽  
Kaiyu Lei ◽  
Rachel M. Tribe ◽  
...  
Keyword(s):  
Preterm Labour ◽  
Elective Caesarean Section ◽  
Oxytocin Receptor ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Myometrial Cells ◽  
Protein Levels ◽  
Repressive Effect ◽  
Effector System ◽  
Cyclase Activator

Our previous work has shown myometrial PKA activity declines in term and twin-preterm labour in association with an increase in the expression of the oxytocin receptor (OTR). Here we investigate the action of cAMP/PKA in basal conditions, with the addition of progesterone (P4) and/or IL-1β to understand how cAMP/PKA acts to maintain pregnancy and whether the combination of cAMP and P4 would be a viable therapeutic combination for the prevention of preterm labour (PTL). Further, given that we have previously found that cAMP enhances P4 action we wanted to test the hypothesis that changes in the cAMP effector system are responsible for the functional withdrawal of myometrial P4 action. Myometrial cells were grown from biopsies obtained from women at the time of elective Caesarean section before the onset of labour. The addition of forskolin, an adenylyl cyclase activator, repressed basal OTR mRNA levels at all doses and P4 only enhanced this effect at its highest dose. Forskolin repressed the IL-1β-induced increase in OTR mRNA and protein levels in a PKA-dependent fashion and repressed IL-1β-activation and nuclear transfer of NFκB and AP-1. P4 had similar effects and the combination P4 and forskolin had greater effects on OTR and NFκB than forskolin alone. While PKA knockdown had no effect on the ability of P4 to repress IL-1β-induced OTR expression it reversed the repressive effect of the combination of P4 and forskolin and resulted in a greater increase than observed with IL-1β alone. These studies suggest that cAMP acts via PKA to repress inflammation-driven OTR expression, but that when PKA activity is reduced, the combination of cAMP and P4 actually enhances the OTR response to inflammation, promoting the onset of labour and suggesting that changes in the cAMP effector system can induce a functional P4 withdrawal.

scholarly journals Anti-Allergic and Anti-Inflammatory Effects of Undecane on Mast Cells and Keratinocytes

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1554
Author(s):  
Dabin Choi ◽  
Wesuk Kang ◽  
Taesun Park
Keyword(s):  
Mast Cells ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Allergic Diseases ◽  
Intracellular Camp ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Skin Conditions ◽  
Factor Α ◽  
Camp Levels

The critical roles of keratinocytes and resident mast cells in skin allergy and inflammation have been highlighted in many studies. Cyclic adenosine monophosphate (cAMP), the intracellular second messenger, has also recently emerged as a target molecule in the immune reaction underlying inflammatory skin conditions. Here, we investigated whether undecane, a naturally occurring plant compound, has anti-allergic and anti-inflammatory activities on sensitized rat basophilic leukemia (RBL-2H3) mast cells and HaCaT keratinocytes and we further explored the potential involvement of the cAMP as a molecular target for undecane. We confirmed that undecane increased intracellular cAMP levels in mast cells and keratinocytes. In sensitized mast cells, undecane inhibited degranulation and the secretion of histamine and tumor necrosis factor α (TNF-α). In addition, in sensitized keratinocytes, undecane reversed the increased levels of p38 phosphorylation, nuclear factor kappaB (NF-κB) transcriptional activity and target cytokine/chemokine genes, including thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and interleukin-8 (IL-8). These results suggest that undecane may be useful for the prevention or treatment of skin inflammatory disorders, such as atopic dermatitis, and other allergic diseases.

scholarly journals Comparison of Two Nasal Cell Collection Methods in Determining Cyclic Adenosine Monophosphate Levels and its Association with Olfaction: A Feasibility Study

2014 ◽  
Vol 5 (1) ◽  
pp. ar.2014.5.0079
Author(s):  
Jack J. Liu ◽  
Guy C. Chan ◽  
Avram S. Hecht ◽  
Daniel R. Storm ◽  
Greg E. Davis
Keyword(s):  
Intraclass Correlation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Olfactory Function ◽  
Secondary Outcome ◽  
Initial Visit ◽  
Two Samples ◽  
Camp Levels ◽  
Collection Methods

Cyclic adenosine monophosphate (cAMP) is a second messenger that may be associated with olfactory function. No known studies have compared existing collection methods for determining nasal cAMP levels. This is a prospective study comparing the comfort and reliability of the nasal curette and cytobrush. A secondary outcome collected for feasibility testing was characterizing the association between cAMP and olfactory function. We enrolled 19 normal olfaction and 10 olfactory dysfunction subjects. Olfaction was measured by the University of Pennsylvania Smell Identification Test. Two samples were obtained from each nasal cavity at the initial visit and at 1 week follow-up. Comfort was measured by a visual analog scale (VAS). cAMP levels were determined by an enzyme immunoassay. For the curette and cytobrush, mean VAS scores were 03 and 0.7 cm (p = 0.48). Intraclass correlation coefficients were 0.81 (curette) and 0.65 (cytobrush) for the initial visit and 0.64 and 0.54 between the initial and follow-up visit. Using the curette, mean cAMP was 537 and 480 fmol/(mg/mL) for the normal and dysfunction cohorts (p = 0.18). Using the cytobrush, cAMP was 505 and 477, respectively (p = 0.65). The curette and cytobrush are both comfortable and reliable collection methods for determining nasal cAMP levels.

Inhibitory action of somatostatin-14 on hormone-stimulated cyclic adenosine monophosphate induction in porcine granulosa and luteal cells

1992 ◽  
Vol 134 (2) ◽  
pp. 297-306 ◽  
Author(s):  
K. Rajkumar ◽  
D. E. Kerr ◽  
R. N. Kirkwood ◽  
B. Laarveld
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Luteal Cells ◽  
Camp Generation ◽  
Camp Induction ◽  
Camp Levels ◽  
Somatostatin 14

ABSTRACT Somatostatin-14 (SRIF-14) inhibited, in a concentration-dependent manner, LH- and forskolin-stimulated cyclic adenosine monophosphate (cAMP) induction in porcine granulosa and luteal cells. The inhibitory effect of SRIF-14 on hormone-induced cAMP generation was more potent in porcine ovarian cells than in the GH-3 pituitary cell line. The inhibitory effect of SRIF-14 was impeded by neutralizing its biological activity with specific antiserum. Preincubation of luteal and granulosa cells with phorbol 12-myristate 13-acetate (PMA) enhanced LH- and forskolin-stimulated cAMP levels. SRIF-14 failed to inhibit LH- or forskolin-stimulated cAMP levels in cells preincubated with PMA. It is concluded that SRIF-14 inhibits hormone-stimulated cAMP induction in the porcine ovary. LH-induced protein kinase C activation may be physiologically important to alleviate the inhibitory effects of SRIF-14. Journal of Endocrinology (1992) 134, 297–306

Cyclic adenosine monophosphate and cyclic guanosine monophosphate variations during isometric tetanus in frog sartorius muscle

1982 ◽  
Vol 60 (1) ◽  
pp. 79-83
Author(s):  
Giorgio Fang ◽  
Giovanni Menchetti ◽  
Giovannella Della Torre ◽  
Lino Volpi ◽  
Teresa Secca ◽  
...  
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Sartorius Muscle ◽  
Tetanic Stimulation ◽  
Frog Sartorius Muscle ◽  
Different Temperatures ◽  
Camp Levels ◽  
Frog Sartorius

Tetanic stimulation at different temperatures (5 and 20 °C) of the frog sartorius muscle results in an increase of cyclic guanosine monophosphate (cGMP) directly correlated to the tension developed. Cyclic adenosine monophosphate (cAMP) levels change differently for different temperature values. The variations could be explained by the interaction between Ca2+ and the enzymes which control cyclic nucleotide levels, namely, adenylate cyclase, guanylate cyclase, and phosphodiesterase.

Systemic effects of cAMP in chemotherapy for Heren’s carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14052-e14052
Author(s):  
Alla Ivanovna Shikhlyarova ◽  
Elena Mikhaylovna Frantsiyants ◽  
Galina Vitalyevna Zhukova ◽  
Natalia D. Cheryarina ◽  
Tatiana Albertovna Barteneva ◽  
...  
Keyword(s):  
Tumor Regression ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Regenerative Processes ◽  
Metabolic Substrates ◽  
Response To Chemotherapy ◽  
Male Wistar Rats ◽  
Camp Levels ◽  
The Brain ◽  
Body Response

e14052 Background: Along with tumor itself, mechanisms of regulation of homeostasis are the target for tumor progression inhibition. The brain, various organs and tumor have different resources of energetic and metabolic substrates. Involvement of cyclic adenosine monophosphate (cAMP) into intimate mechanisms of proliferation, hormonal and energetic homeostasis indicates the possibility to use this factor in chemotherapy of tumors to improve the resistance of the organism. The purpose of the study was to analyze levels of endogenous cAMP in tumor and in organs as a criterium of systemic body response to chemotherapy with cAMP application. Methods: The study included 56 male Wistar rats with Heren’s carcinoma receiving peritumoral injections of cyclophosphan (CP) 50 mcg/kg (Baxter Oncology GmbH, Germany) alone and in combination with cAMP (Sigma-Aldrich, USA), P.O. at a concentration of 0.01%. cAMP levels in homogenates of organs and tumors were measured by immunoradiometric assay (Immunotech, Czech Republic) using Arian radiometer (Vitaco, Russia). Data were processed using Statistica 6. Results: cAMP levels in growing tumors in rats without treatment (the control) were maximal (7.03±1.5 nmol/L). CP injections alone during inhibition of carcinoma growth allowed the reduction of tumor cAMP level by 3.3 times. Combination of CP and cAMP resulted in tumor regression, and endogenous cAMP levels in tumor decreased by 10 times compared with the control. Similar dynamics of cAMP reductions was noted in the adrenal glands. The lungs, thymus, lymph nodes and especially the testes and the brain, on the contrary, showed accumulation of cAMP to the normal levels and higher. Conclusions: The range of cAMP levels in organs and tumors of rats receiving combination of CP and cAMP demonstrated the development of adaptive and regenerative processes in organs responsible for the neuroendocrine regulation, suppression of stimulation of stress-realizing systems and metabolic support of the processes of increasing non-specific antitumor resistance along with inhibited proliferative activity of tumors.

Effect of exogenous hydrogen peroxide on iodide transport and iodine organification in FRTL-5 rat thyroid cells

1993 ◽  
Vol 129 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Ge Chen ◽  
A Eugene Pekary ◽  
Masahiro Sugawara ◽  
Jerome M Hershman
Keyword(s):  
Hydrogen Peroxide ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Thyroid Peroxidase ◽  
Thyroid Cells ◽  
Iodide Transport ◽  
Biphasic Effect ◽  
Rat Thyroid ◽  
Camp Levels ◽  
Hormone Formation

Hydrogen peroxide plays an important role in the regulation of iodination and thyroid hormone formation. In the present study, the effect of exogenous H2O2 on 125I transport and organification was investigated in FRTL-5 rat thyroid cells. Less than 20 passages after subcloning, cells in 24-well plates (6 × 104 cells/well) were maintained in a thyrotropin (TSH)-containing medium (6H) for 3 days. A TSH-free medium (5H) was then used for the next 7 days. A 1-h exposure to H2O2 stimulated 125I transport and 125I organification at 0.1–0.5 mmol/l H2O2 and had a toxic effect on FRTL-5 cells at 5 mmol/l. Hydrogen peroxide (0.5 mmol/l) augmented the iodide transport and iodine organification induced by TSH (333U/l) by two- and threefold, respectively. The biphasic effect of H2O2 was blocked totally by 5–200 μg/l of catalase. Catalase by itself did not influence TSH-mediated 125I transport and 125I organification. Hydrogen peroxide (0.5 mmol/l) added to cells in 5H medium increased Na+K+-ATPase activity twofold. Ouabain (1 mmol/l), an inhibitor of Na+K +-ATPase, completely inhibited the twofold increase in 125I transport induced by 0.5 mmol/l H2O2 but only inhibited H2O2-induced 125I organification by 28%. Methimazole (1 mmol/l), an inhibitor of thyroid peroxidase, had no effect on H2O2-mediated 125I transport but totally blocked the fivefold rise in 125I organification induced by 0.5 mmol/1 H2O2. The effect of H2O2 on intracellular cyclic adenosine monophosphate (cAMP) levels also was studied. Hydrogen peroxide (0.5 mmol/l) decreased baseline and 160 mU/l TSH-induced cAMP levels by 35 and 87%, respectively, while a 3-h incubation with 0.5 mmol/l H2O2 increased Na + K +-ATPase in 5H and 6H media. We conclude that H2O2 plays an important role in the regulation of iodide transport and organification and also may affect signal transduction and the electrochemical gradient in thyroid cells. Our results also provide evidence that functional thyroid peroxidase activity is present in FRTL-5 cells.

Initial accumulation of platelets during arterial thrombus formation in vivo is inhibited by elevation of basal cAMP levels

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2127-2134 ◽  
Author(s):  
Derek S. Sim ◽  
Glenn Merrill-Skoloff ◽  
Barbara C. Furie ◽  
Bruce Furie ◽  
Robert Flaumenhaft
Keyword(s):  
Vascular Injury ◽  
Intracellular Signaling ◽  
Thrombus Formation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
In Vivo Model ◽  
The Status ◽  
Platelet Accumulation ◽  
Camp Levels

Abstract Platelet accumulation at sites of vascular injury is the primary event in arterial thrombosis. Initial platelet accrual into thrombi is mediated by interactions of platelet adhesion receptors with ligands on the injured endothelium or in the sub-endothelial matrix. The role of intracellular signals in initial platelet accumulation at sites of endothelial injury, however, is the subject of debate. We have used a newly discovered inhibitor of phosphodiesterase 3A (PDE3A) and the well-characterized PDE3A inhibitor, cilostazol, to modulate 3′,5′-cyclic adenosine monophosphate (cAMP) levels in an in vivo model that enables the kinetic analysis of platelet accumulation. These studies demonstrate that elevation of basal cAMP levels results in an overall decline in platelet accumulation at the site of vascular injury. In particular, the initial rate of accumulation of platelets is inhibited by elevation of cAMP. Analysis of the kinetics of individual platelets at injury sites using intravital microscopy demonstrates that cAMP directs the rate at which platelets attach to and detach from thrombi. These studies demonstrate that cAMP in circulating platelets controls attachment to and detachment from sites of arteriolar injury. Thus, the status of the intracellular signaling machinery prior to engagement of platelet receptors influences the rate of platelet accumulation during thrombus formation.

scholarly journals Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kerstin Johann ◽  
Toszka Bohn ◽  
Fatemeh Shahneh ◽  
Natascha Luther ◽  
Alexander Birke ◽  
...  
Keyword(s):  
Immune Cells ◽  
Antitumor Immunity ◽  
Immune Escape ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Benzyl Ester ◽  
Receptor Expression ◽  
Single Cell Sequencing ◽  
Copolymer Micelles ◽  
Toxic Concentrations

AbstractThe acidic tumor microenvironment in melanoma drives immune evasion by up-regulating cyclic adenosine monophosphate (cAMP) in tumor-infiltrating monocytes. Here we show that the release of non-toxic concentrations of an adenylate cyclase (AC) inhibitor from poly(sarcosine)-block-poly(L-glutamic acid γ-benzyl ester) (polypept(o)id) copolymer micelles restores antitumor immunity. In combination with selective, non-therapeutic regulatory T cell depletion, AC inhibitor micelles achieve a complete remission of established B16-F10-OVA tumors. Single-cell sequencing of melanoma-infiltrating immune cells shows that AC inhibitor micelles reduce the number of anti-inflammatory myeloid cells and checkpoint receptor expression on T cells. AC inhibitor micelles thus represent an immunotherapeutic measure to counteract melanoma immune escape.

Sign in / Sign up

Export Citation Format

Share Document