Degradation of the Cyclic AMP Antagonist Prostaglandylinositol Cyclic Phosphate (Cyclic PIP) by Dephosphorylation

1999 ◽  
Vol 380 (1) ◽  
Author(s):  
A. Kassner ◽  
M. Lessmann ◽  
H.K. Wasner
Keyword(s):  
Cyclic Amp ◽  
Inositol Phosphate ◽  
Prostaglandin E ◽  
Rat Tissues ◽  
Degrading Enzyme ◽  
Cyclic Phosphate ◽  
The Difference ◽  
Synthesis And Degradation

AbstractThe cAMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is synthesized from prostaglandin E and activated inositol phosphate. From various tissues only that amount of cyclic PIP can be isolated that constitutes the difference between synthesis and degradation. In order to overcome this drawback, the cyclic PIP degrading enzyme or enzymes had to be characterized prior to searching for inhibitors. Cyclic PIP degrading activities have been found in all rat tissues tested, and are lowest in brain (380 pmol × min

Properties of an Adenosine Cyclic Phosphates Degrading Enzyme in Nicotiana tabacum L. var. Xanthi

1977 ◽  
Vol 32 (3-4) ◽  
pp. 297-300 ◽  
Author(s):  
Axel Brennicke ◽  
Hans Dieter Frey
Keyword(s):  
Nicotiana Tabacum ◽  
Cyclic Amp ◽  
Inorganic Phosphate ◽  
Strong Inhibitor ◽  
Degrading Enzyme ◽  
Nicotiana Tabacum L ◽  
Messenger System ◽  
Cyclic Phosphate ◽  
Act Up ◽  
Cyclic Phosphates

Abstract This work describes an enzyme which degrades adenosine 3′:5′-cyclic phosphate (3′ :5′-cyclic-AMP) and adenosine 2′:3′-cyclic phosphate (2′:3′-cyclic-AMP). The reaction pro­ ducts are 3′-AMP and 5′-AMP in case of 3′:5′-cyclic-AMP, 2′-AMP and 3′-AMP when 2′:3′-cyclic-AMP is given as substrate. Inorganic phosphate acts as a strong inhibitor, whereas theophyllin does not act up to a concentration of 10-3 m . Probably the adenosine cyclic phosphates degrading enzyme has no function in a ‘second messenger’ system with 3′:5′-cyclic-AMP.

The effect of glucagon and prostaglandin E1 on cyclic AMP levels in liver of heat exposed hamsters

1980 ◽  
Vol 93 (4) ◽  
pp. 475-478 ◽  
Author(s):  
Miriam Aharon ◽  
Yosef Graziani ◽  
Reuben Chayoth
Keyword(s):  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Prostaglandin E1 ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Prostaglandin E ◽  
Liver Slices ◽  
Presence And Absence ◽  
The Difference

Abstract. Cyclic AMP levels in liver slices of hamsters exposed to 35°C for 21 days and controls maintained at 22°C was found to be similar in basal conditions. Glucagon (10 μg/ml) caused 3.5 times elevation of cyclic AMP levels in control hamsters and 9 times elevation in 35°C exposed hamsters, thus a difference of 150% of the nucleotide concentration was found between the two experimental groups. When 10−2m theophylline was added, the cyclic AMP levels were 80% higher in 35°C exposed hamsters both in the presence and absence of 10 μg/ml glucagon. The difference between controls and heat exposed animals was found to be the same when various concentrations of both glucagon or prostaglandin E1 were added to the liver slices. Adenylate cyclase activity was similar in both experimental groups, while low Km phosphodiesterase was significantly less active in the liver of 35°C exposed animals when compared to the controls.

Interaction between parathyroid hormone and prostaglandin E1 on cyclic AMP metabolism in rat kidney

1980 ◽  
Vol 93 (3) ◽  
pp. 339-345 ◽  
Author(s):  
Naokazu Nagata ◽  
Yuriko Ono ◽  
Narimichi Kimura
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Adenylate Cyclase ◽  
Rat Kidney ◽  
Prostaglandin E ◽  
Cortical Tissue ◽  
Newborn Rat ◽  
Simultaneous Addition ◽  
Renal Cortical Tissue ◽  
Subsequent Addition

Abstract. The interaction between parathyroid hormone (PTH) and prostaglandin E1 (PGE1) in influencing cyclic AMP metabolism in rat renal cortical tissue was examined. PTH and PGE1 stimulated additively the adenylate cyclase activity in the homogenate of the tissue. Both PTH and PGE1 enhanced the level of cyclic AMP in the incubated renal cortical tissue, but the effect of their simultaneous addition did not exceed the effect induced by PTH alone. Cyclic AMP accumulated in the incubation medium by stimulation by PTH was decreased by the simultaneous addition of PGE1. When the tissue was pre-incubated for 30 min with 2 to 10 μg/ml of PGE1, the magnitude of the increase of cyclic AMP caused by PTH subsequently added was lessened. However, the response to PTH of adenylate cyclase preparation obtained from the homogenate of PGE1-pre-treated tissue was not decreased. When first PTH was added to the incubating renal cortical tissue, the subsequent addition of PGE1 accelerated the decrease of cyclic AMP content in the tissue and decreased the amount of cyclic AMP released from the tissue. The interaction of PTH and PGE1 on cyclic AMP metabolism in the renal cortical tissue was in contrast to that seen in newborn rat calvaria where PGE1 and PTH acted additively in enhancing the level of cyclic AMP.

Prostaglandin E1 as an Intercellular Regulator of Cyclic AMP Levels

Pathobiology ◽  
1976 ◽  
Vol 44 (3-6) ◽  
pp. 260-277 ◽  
Author(s):  
Vittorio Tomasi
Keyword(s):  
Cyclic Amp ◽  
Prostaglandin E

scholarly journals Age-related changes in collagen synthesis and degradation in rat tissues. Importance of degradation of newly synthesized collagen in regulating collagen production

1991 ◽  
Vol 276 (2) ◽  
pp. 307-313 ◽  
Author(s):  
P K Mays ◽  
R J McAnulty ◽  
J S Campa ◽  
G J Laurent
Keyword(s):  
Skeletal Muscle ◽  
Collagen Synthesis ◽  
Rat Tissues ◽  
Age Related ◽  
Developmental Growth ◽  
Cross Links ◽  
Fractional Synthesis ◽  
Synthesis And Degradation ◽  
Age Related Changes

During developmental growth, collagens are believed to be continuously deposited into an extracellular matrix which is increasingly stabilized by the formation of covalent cross-links throughout life. However, the age-related changes in rates of synthetic and degradative processes are less well understood. In the present study we measured rates of collagen synthesis in vivo using a flooding dose of unlabelled proline given with [14C]proline and determining production of hydroxy[14C]proline. Degradation of newly synthesized collagen was estimated from the amount of free hydroxy [14C]proline in tissues 30 min after injection. Collagen fractional synthesis rates ranged from about 5%/day in skeletal muscle to 20%/day in hearts of rats aged 1 month. At 15 months of age, collagen fractional synthesis rates had decreased markedly in lung and skin, but in skeletal muscle and heart, rates were unchanged. At 24 months of age, synthesis rates had decreased by at least 10-fold in all tissues, compared with rates at 1 month. The proportion of newly synthesized collagen degraded ranged from 6.4 +/- 0.4% in skin to 61.6 +/- 5.0% in heart at 1 month of age. During aging the proportion degraded increased in all tissues to maximal values at 15 months, ranging from 56 +/- 7% in skin to 96 +/- 1% in heart. These data suggest that there are marked age-related changes in rates of collagen metabolism. They also indicate that synthesis is active even in old animals, where the bulk of collagens produced are destined to be degraded.

scholarly journals Phosphorylation of β-Catenin by Cyclic AMP-Dependent Protein Kinase Stabilizes β-Catenin through Inhibition of Its Ubiquitination

2005 ◽  
Vol 25 (20) ◽  
pp. 9063-9072 ◽  
Author(s):  
Shin-ichiro Hino ◽  
Chie Tanji ◽  
Keiichi I. Nakayama ◽  
Akira Kikuchi
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Wnt Signaling ◽  
Protein Level ◽  
Glycogen Synthase ◽  
Wnt Signaling Pathway ◽  
Prostaglandin E ◽  
Dependent Protein Kinase ◽  
Intact Cells ◽  
Dependent Protein

ABSTRACT The mechanism of cross talk between the Wnt signaling and cyclic AMP (cAMP)-dependent protein kinase (protein kinase A [PKA]) pathways was studied. Prostaglandin E1 (PGE1), isoproterenol, and dibutyryl cAMP (Bt2cAMP), all of which activate PKA, increased the cytoplasmic and nuclear β-catenin protein level, and these actions were suppressed by a PKA inhibitor and RNA interference for PKA. PGE1 and Bt2cAMP also increased T-cell factor (Tcf)-dependent transcription through β-catenin. Bt2cAMP suppressed degradation of β-catenin at the protein level. Although PKA did not affect the formation of a complex between glycogen synthase kinase 3β (GSK-3β), β-catenin, and Axin, phosphorylation of β-catenin by PKA inhibited ubiquitination of β-catenin in intact cells and in vitro. Ser675 was found to be a site for phosphorylation by PKA, and substitution of this serine residue with alanine in β-catenin attenuated inhibition of the ubiquitination of β-catenin by PKA, PKA-induced stabilization of β-catenin, and PKA-dependent activation of Tcf. These results indicate that PKA inhibits the ubiquitination of β-catenin by phosphorylating β-catenin, thereby causing β-catenin to accumulate and the Wnt signaling pathway to be activated.

A randomized clinical efficacy study targeting mPGES1 or EP4 in dogs with spontaneous osteoarthritis

2019 ◽  
Vol 11 (516) ◽  
pp. eaaw9993
Author(s):  
Carol Robertson-Plouch ◽  
John R. Stille ◽  
Peng Liu ◽  
Claire Smith ◽  
Dorothy Brown ◽  
...  
Keyword(s):  
Posterior Probability ◽  
Brief Pain Inventory ◽  
Repeated Measure ◽  
Controlled Study ◽  
Prostaglandin E ◽  
Double Blind ◽  
Mixed Effect ◽  
Secondary Endpoints ◽  
Efficacy Measures ◽  
The Difference

Canine studies of spontaneous osteoarthritis (OA) pain add valuable data supporting drug treatment mechanisms that may translate to humans. A multicenter, randomized, double-blind, placebo- and active-controlled study was conducted in client-owned dogs with moderate OA pain to evaluate efficacy of LYA, an inhibitor of microsomal prostaglandin E synthase-1 (mPGES1), an EP4 antagonist (LYB), and carprofen, versus placebo. Of 255 dogs screened, 163 were randomized (placebo/LYA/LYB/carprofen: n = 43/39/42/39) and 158 completed treatment. Efficacy versus placebo was assessed using Bayesian mixed-effect model for repeated measure analyses of the Canine Brief Pain Inventory (CBPI) pain interference score (PIS; primary endpoint), pain severity score, and overall impression, as well as the Liverpool Osteoarthritis in Dogs (LOAD) mobility score. The posterior probability that the difference to placebo was <0 at week 2 was 80% for LYA and 54% for LYB for CBPI PIS (both <95% predefined threshold). For secondary endpoints, the posterior probability that the difference to placebo was <0 at week 2 ranged from 89 to 96% for LYA and from 56 to 89% for LYB. The posterior probabilities comparing carprofen to placebo groups were ≥90% for all efficacy endpoints. The proportion of dogs with one or more adverse event was not significantly different from placebo (32.6%) for LYA (35.9%) or carprofen (25.6%), but the rate for LYB (59.5%) was higher versus placebo (P = 0.017). LYA treatment demonstrated consistent improvement in all efficacy measures, suggesting that inhibition of mPGES1 may be an effective treatment for chronic pain associated with OA.

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