Disease relevance of Cyclic AMP

• The control of melanin production, tyrosinase activity, and cell replication by melanocyte-stimulating hormone (MSH) and cyclic AMP (cAMP) was examined in differentially metastasizing B16 mouse melanoma variants [1].
• Several types of adrenocortical tumors that lead to Cushing syndrome may be caused by aberrant cyclic AMP (cAMP) signaling [2].
• Cyclic AMP (cAMP) causes growth arrest in G1 and induction of cAMP phosphodiesterase and decrease of ornithine decarboxylase in S49 mouse lymphoma cells [3].
• In contrast to what found in neurons, the D(1)-dependent cAMP formation in striatal astrocytes is partially reduced by pertussis toxin (PTX) treatment [4].
• These neuroblastoma cells respond to cAMP by forming neurite-like extensions [5].
• We conclude that cAMP signaling is pivotal in regulating the adipogenic effect of n-6 PUFAs and that diet-induced differences in cAMP levels may explain the ability of n-6 PUFAs to either enhance or counteract adipogenesis and obesity [6].

Psychiatry related information on Cyclic AMP

• Gel shift assays also showed the decrease of cAMP-response element (CRE)-binding activity relating to cAMP activity in the frontal cortex and hippocampus of learned helplessness rats on Days 1 and 7 [7].

High impact information on Cyclic AMP

• Finally, cAMP restored both RA-triggered differentiation and PML-RARA transcriptional activation in mutant RA-resistant APL cells [8].
• Collectively, our findings directly demonstrate that APL cell differentiation parallels transcriptional activation through PML-RARA-RXR oligomers and that those are functionally targeted by cAMP, identifying this agent as another oncogene-targeted therapy [8].
• These findings show that netrin-1 responsiveness is developmentally regulated and suggest that intrinsic changes that lower cAMP levels underlie this regulation [9].
• Platelet-derived growth factor and fibroblast growth factor differentially regulate interleukin 1beta- and cAMP-induced nitric oxide synthase expression in rat renal mesangial cells [10].
• Histamine stimulated cyclic AMP (cAMP) accumulation in cultured mesangial cells (64.0 +/- 22.1 to 511.4 +/- 86.6 pmol/mg protein, n = 9) but had no effect on cAMP accumulation in epithelial cells [11].

Chemical compound and disease context of Cyclic AMP

• P1-mediated responses of PI turnover and cAMP formation are not present in C6 glioma cells [12].
• Pertussis toxin (PTX) blocked the nucleotide-induced inhibition of cAMP accumulation but exerted no effect on inositol phosphate formation [12].
• Proximal promoter of the rat brain creatine kinase gene lacks a consensus CRE element but is essential for the cAMP-mediated increased transcription in glioblastoma cells [13].
• The inhibitory effect of GABA on cAMP levels was mimicked by the GABAB receptor agonist baclofen (100 microM) and totally abolished by a 4-h pretreatment with pertussis toxin (0.1 microgram/ml) [14].
• Urinary excretion of cyclic GMP (cGMP) and the plasma level of cyclic AMP (cAMP) were determined in patients with liver diseases [15].

Biological context of Cyclic AMP

• The molecular target or targets of cGMP in erectile tissue and the role of cAMP for normal penile erection are not known [16].
• However, a promoter deletion to -68, which removes the proximal cAMP regulatory element, was unresponsive to added protein kinase catalytic subunit [17].
• Mutation of the TATA box resulted in a 94% decrease in the level of transcription noted with the intact promoter, while sequence substitutions within the proximal cAMP regulatory element decreased the transcription rate to 25% [17].
• These results indicate that a representative set of Dictyostelium aggregation stage genes are under transcriptional control; both the transcription and the stability of these mRNAs require either continued cell-to-cell interactions or cAMP [18].
• A cAMP/CAP binding site is located at -40.5, and activation by cAMP/CAP is shown to be typical of a class II promoter [19].

Anatomical context of Cyclic AMP

• Site-selective cAMP analogs at micromolar concentrations induce growth arrest and differentiation of acute promyelocytic, chronic myelocytic, and acute lymphocytic human leukemia cell lines [20].
• These findings demonstrate a collaboration between cAMP signaling and cyclin D1 in the ligand-independent activation of ER-mediated transcription in mammary epithelial cells and show that the functional associations of cyclin D1 are regulated as a function of cellular context [21].
• Here we report that serum-stimulated hyperphosphorylation of Raf-1 was inhibited by TSH treatment of Wistar rat thyroid cells, indicating that in this cell line, as in other cell types, increases in intracellular cAMP levels inhibit activation of downstream kinases targeted by Ras [22].
• Cholera toxin and dibutyryl cyclic AMP (cAMP) also induced mast cells [23].
• The results suggest that bifunctional AKAP 150 tethers PKAII beta to the dendritic cytoskeleton, thereby creating a discrete target site for the reception and propagation of signals carried by cAMP [24].

Associations of Cyclic AMP with other chemical compounds

• We conclude that endogenous arachidonate metabolism regulates mesangial cell contraction through elevation of intracellular cAMP [25].
• R804H and R867G were frequent among patients with adrenocortical tumors; although statistical significance was not reached, these variants affected significantly enzymatic function in vitro with variable increases in cAMP and/or cyclic guanosine 3',5'-monophosphate levels in HeLa and HEK293 cells [2].
• Furthermore, mast cell induction by PGE was dose-dependently suppressed by inhibitors for cAMP-dependent A kinase [23].
• With isoprenaline, the cAMP concentration and the glycerol production was significantly higher in the diabetic adipose tissue [26].
• The results suggest the presence of regulatory pathways important in chondrogenesis which occur independent of those initiated by PGE2 and the cAMP system [27].
• In lung fibroblasts, inhibition of the TGFbeta1-stimulated CCN2/CTGF by PGE(2), butaprost, or forskolin is due to p38, ERK, and JNK MAP kinase inhibition that is cAMP-dependent [28].
• The CFTR inhibitors DPC, GlyH-101 and CFTRinh-172 all significantly reduced the cAMP-activated glycerol-induced cell swelling [29].
• Additional experiments revealed that neither 2MeSAMP nor ARC69931MX (cangrelor) increased cAMP through activation of A2a, IP, DP, or EP2 receptors, which are known to couple to Gs [30].
• Taken together, our results strengthen the support for a key role of melanosome pH in the regulation of melanin synthesis and, for the first time, demonstrate that melanosome pH is regulated by cAMP and alphaMSH [31].

Gene context of Cyclic AMP

• These results indicate that cAMP and cGMP inhibit ET-1-induced activation of MAPK in cultured mesangial cells at different steps; the former might inhibit at a step downstream of PKC and the latter prior to PKC [32].
• Dibutyryl cAMP (Bt2-cAMP) and 8-bromo-cGMP (8-Br-cGMP), cell permeable analogues of cAMP and cGMP, were also able to inhibit the activation of MAPK and MAPK kinase (MAPKK) by ET-1 without interfering basal activities [32].
• Similarly to the liver, the molecular mechanism of cAMP/protein kinase A regulation involves cAMP-response element-binding protein, HNF4alpha, CAAT/enhancer-binding protein, and HNF1 [33].
• An Akt inhibitor blocked PDE3A activation and constrained thrombin-induced cAMP reduction [34].
• Pituitary adenylate cyclase-activating polypeptide increased cAMP levels and stimulated GLP-1 release from GLUTag cells [35].
• We show that activation of Epac by specific cAMP analogs or by the pituitary adenylate cyclase-activating polypeptide induces a potent activation of the Ca2+-sensitive big K+ channel, slight membrane hyperpolarization, and increased after-hyperpolarization in cultured cerebellar granule cells [36].
• Knockdown of C/EBPbeta and -delta isoforms abolished both SOCS-3 induction and inhibition of IL-6 signaling in response to cAMP [37].
• We report that the second messenger cAMP inhibits the migration of mouse embryonic fibroblast cells and mouse breast tumor cells. cAMP acts downstream of the small GTPase Rac and interferes with the formation of lamellipodia [38].
• We report that Epac acts synergistically with PKA in cAMP-mediated mitogenesis [39].
• Our results provide a molecular mechanism by which cAMP suppresses JNK activation and antagonizes apoptosis [40].
• The activation of the ERK1/2 and Akt pathways as well as the expression of EGFR was stimulated by reagents that elevate intracellular cAMP levels, via cAMP analog 8-bromo-cAMP and AC activator forskolin [41].

Analytical, diagnostic and therapeutic context of Cyclic AMP

• 5. MJ33 incorporated into unilamellar liposomes (dipalmitoyl PC/egg PC/cholesterol/phosphatidylglycerol, molar proportions 10:5:3:2) or co-sonicated with biosynthesized natural surfactant was instilled into the trachea of the anaesthetized rat; lungs were then removed for 2 h perfusion in the absence or presence of 0.1 mM-8-bromo cAMP [42].
• These events were partially eliminated when infected astrocytes were treated with aspirin and cocultures were treated with anti-IL-10 neutralizing antibodies and RP-8-Br cyclic AMP (cAMP), a protein kinase A inhibitor [43].
• This report shows that the addition of each individual polyamine to confluent and serum-restricted heart cell cultures, while lowering cAMP content, induces an early and rapid increase of cGMP content by reducing the rate of its degradation [44].
• During a time course of 96 h, cell morphologies were determined by light microscopy, cellular cAMP levels measured by radioimmunoassay, and IRBP and b-actin gene expression determined by Northern blot and RNase protection analyses [45].
• Cyclic AMP (cAMP) was measured by enzyme immunoassay [46].

References