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Chemical Compound Review

Cyclic AMP     (1S,6R,8R,9R)-8-(6- aminopurin-9-yl)-3...

Synonyms: Acrasin, cAMP, SureCN1244, CHEMBL316966, CCRIS 4291, ...
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Disease relevance of Cyclic AMP


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


Chemical compound and disease context of Cyclic AMP


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].


  1. Control of melanogenesis in mouse melanoma cells of varying metastatic potential. Niles, R.M., Makarski, J.S. J. Natl. Cancer Inst. (1978) [Pubmed]
  2. Adrenal hyperplasia and adenomas are associated with inhibition of phosphodiesterase 11A in carriers of PDE11A sequence variants that are frequent in the population. Horvath, A., Giatzakis, C., Robinson-White, A., Boikos, S., Levine, E., Griffin, K., Stein, E., Kamvissi, V., Soni, P., Bossis, I., de Herder, W., Carney, J.A., Bertherat, J., Gregersen, P.K., Remmers, E.F., Stratakis, C.A. Cancer Res. (2006) [Pubmed]
  3. Regulation of phosphodiesterase and ornithine decarboxylase by cAMP is cell cycle independent. Kaiser, N., Bourne, H.R., Insel, P.A., Coffino, P. J. Cell. Physiol. (1979) [Pubmed]
  4. Pharmacological and molecular evidence for dopamine D(1) receptor expression by striatal astrocytes in culture. Zanassi, P., Paolillo, M., Montecucco, A., Avvedimento, E.V., Schinelli, S. J. Neurosci. Res. (1999) [Pubmed]
  5. A cAMP-activated pathway, including PKA and PI3K, regulates neuronal differentiation. Sánchez, S., Jiménez, C., Carrera, A.C., Diaz-Nido, J., Avila, J., Wandosell, F. Neurochem. Int. (2004) [Pubmed]
  6. cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids. Madsen, L., Pedersen, L.M., Liaset, B., Ma, T., Petersen, R.K., van den Berg, S., Pan, J., Müller-Decker, K., Dülsner, E.D., Kleemann, R., Kooistra, T., Døskeland, S.O., Kristiansen, K. J. Biol. Chem. (2008) [Pubmed]
  7. Different regulation of adenylyl cyclase and rolipram-sensitive phosphodiesterase activity on the frontal cortex and hippocampus in learned helplessness rats. Itoh, T., Abe, K., Tokumura, M., Horiuchi, M., Inoue, O., Ibii, N. Brain Res. (2003) [Pubmed]
  8. PML-RARA-RXR oligomers mediate retinoid and rexinoid/cAMP cross-talk in acute promyelocytic leukemia cell differentiation. Kamashev, D., Vitoux, D., De Thé, H. J. Exp. Med. (2004) [Pubmed]
  9. Age-related changes underlie switch in netrin-1 responsiveness as growth cones advance along visual pathway. Shewan, D., Dwivedy, A., Anderson, R., Holt, C.E. Nat. Neurosci. (2002) [Pubmed]
  10. Platelet-derived growth factor and fibroblast growth factor differentially regulate interleukin 1beta- and cAMP-induced nitric oxide synthase expression in rat renal mesangial cells. Kunz, D., Walker, G., Eberhardt, W., Messmer, U.K., Huwiler, A., Pfeilschifter, J. J. Clin. Invest. (1997) [Pubmed]
  11. Histamine modulates contraction and cyclic nucleotides in cultured rat mesangial cells. Differential effects mediated by histamine H1 and H2 receptors. Sedor, J.R., Abboud, H.E. J. Clin. Invest. (1985) [Pubmed]
  12. Different signal transduction pathways are coupled to the nucleotide receptor and the P2Y receptor in C6 glioma cells. Lin, W.W., Chuang, D.M. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  13. 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. Kuzhikandathil, E.V., Molloy, G.R. J. Neurosci. Res. (1999) [Pubmed]
  14. Mechanism of action of gamma-aminobutyric acid on frog melanotrophs. Desrues, L., Vaudry, H., Lamacz, M., Tonon, M.C. J. Mol. Endocrinol. (1995) [Pubmed]
  15. Increased excretion of urinary cyclic GMP in primary hepatoma and preneoplastic liver. Shimamura, J., Taketa, K., Ito, T., Shimada, Y., Nagashima, H. Acta Med. Okayama (1982) [Pubmed]
  16. Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. Hedlund, P., Aszodi, A., Pfeifer, A., Alm, P., Hofmann, F., Ahmad, M., Fassler, R., Andersson, K.E. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  17. In vitro analysis of promoter elements regulating transcription of the phosphoenolpyruvate carboxykinase (GTP) gene. Klemm, D.J., Roesler, W.J., Liu, J.S., Park, E.A., Hanson, R.W. Mol. Cell. Biol. (1990) [Pubmed]
  18. Transcriptional control of gene expression during development of Dictyostelium discoideum. Landfear, S.M., Lefebvre, P., Chung, S., Lodish, H.F. Mol. Cell. Biol. (1982) [Pubmed]
  19. Control of the expression of the manXYZ operon in Escherichia coli: Mlc is a negative regulator of the mannose PTS. Plumbridge, J. Mol. Microbiol. (1998) [Pubmed]
  20. Site-selective cAMP analogs at micromolar concentrations induce growth arrest and differentiation of acute promyelocytic, chronic myelocytic, and acute lymphocytic human leukemia cell lines. Tortora, G., Tagliaferri, P., Clair, T., Colamonici, O., Neckers, L.M., Robins, R.K., Cho-Chung, Y.S. Blood (1988) [Pubmed]
  21. Regulation of the functional interaction between cyclin D1 and the estrogen receptor. Lamb, J., Ladha, M.H., McMahon, C., Sutherland, R.L., Ewen, M.E. Mol. Cell. Biol. (2000) [Pubmed]
  22. Thyrotropin-induced mitogenesis is Ras dependent but appears to bypass the Raf-dependent cytoplasmic kinase cascade. al-Alawi, N., Rose, D.W., Buckmaster, C., Ahn, N., Rapp, U., Meinkoth, J., Feramisco, J.R. Mol. Cell. Biol. (1995) [Pubmed]
  23. An essential role of prostaglandin E on mouse mast cell induction. Hu, Z.Q., Asano, K., Seki, H., Shimamura, T. J. Immunol. (1995) [Pubmed]
  24. cAMP signaling in neurons: patterns of neuronal expression and intracellular localization for a novel protein, AKAP 150, that anchors the regulatory subunit of cAMP-dependent protein kinase II beta. Glantz, S.B., Amat, J.A., Rubin, C.S. Mol. Biol. Cell (1992) [Pubmed]
  25. Eicosanoids and control of mesangial cell contraction. Mené, P., Dunn, M.J. Circ. Res. (1988) [Pubmed]
  26. Abnormalities in the adrenergic control and the rate of lipolysis in isolated human subcutaneous adipose tissue in diabetes mellitus. Arner, P., Ostman, J. Diabetologia (1976) [Pubmed]
  27. Phorbol esters inhibit chondrogenesis in limb mesenchyme by mechanisms independent of PGE2 or cyclic AMP1. Biddulph, D.M., Dozier, M.M. Exp. Cell Res. (1989) [Pubmed]
  28. Tissue-specific mechanisms for CCN2/CTGF persistence in fibrotic gingiva: interactions between cAMP and MAPK signaling pathways, and prostaglandin E2-EP3 receptor mediated activation of the c-JUN N-terminal kinase. Black, S.A., Palamakumbura, A.H., Stan, M., Trackman, P.C. J. Biol. Chem. (2007) [Pubmed]
  29. Role of NHERF1, cystic fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9. Pietrement, C., Da Silva, N., Silberstein, C., James, M., Marsolais, M., Van Hoek, A., Brown, D., Pastor-Soler, N., Ameen, N., Laprade, R., Ramesh, V., Breton, S. J. Biol. Chem. (2008) [Pubmed]
  30. The P2Y12 antagonists, 2-methylthioadenosine 5'-monophosphate triethylammonium salt and cangrelor (ARC69931MX), can inhibit human platelet aggregation through a Gi-independent increase in cAMP levels. Srinivasan, S., Mir, F., Huang, J.S., Khasawneh, F.T., Lam, S.C., Le Breton, G.C. J. Biol. Chem. (2009) [Pubmed]
  31. {alpha}MSH and Cyclic AMP elevating agents control melanosome pH through a protein kinase A-independent mechanism. Cheli, Y., Luciani, F., Khaled, M., Beuret, L., Bille, K., Gounon, P., Ortonne, J.P., Bertolotto, C., Ballotti, R. J. Biol. Chem. (2009) [Pubmed]
  32. Differential inhibition of mesangial MAP kinase cascade by cyclic nucleotides. Haneda, M., Araki, S., Sugimoto, T., Togawa, M., Koya, D., Kikkawa, R. Kidney Int. (1996) [Pubmed]
  33. Transcriptional regulation of the glucose-6-phosphatase gene by cAMP/vasoactive intestinal peptide in the intestine. Role of HNF4alpha, CREM, HNF1alpha, and C/EBPalpha. Gautier-Stein, A., Zitoun, C., Lalli, E., Mithieux, G., Rajas, F. J. Biol. Chem. (2006) [Pubmed]
  34. Thrombin regulates intracellular cyclic AMP concentration in human platelets through phosphorylation/activation of phosphodiesterase 3A. Zhang, W., Colman, R.W. Blood (2007) [Pubmed]
  35. Cyclic AMP triggers glucagon-like peptide-1 secretion from the GLUTag enteroendocrine cell line. Simpson, A.K., Ward, P.S., Wong, K.Y., Collord, G.J., Habib, A.M., Reimann, F., Gribble, F.M. Diabetologia (2007) [Pubmed]
  36. Exchange protein activated by cAMP (Epac) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons. Ster, J., De Bock, F., Guérineau, N.C., Janossy, A., Barrère-Lemaire, S., Bos, J.L., Bockaert, J., Fagni, L. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  37. Identification of CCAAT/enhancer-binding proteins as exchange protein activated by cAMP-activated transcription factors that mediate the induction of the SOCS-3 gene. Yarwood, S.J., Borland, G., Sands, W.A., Palmer, T.M. J. Biol. Chem. (2008) [Pubmed]
  38. cAMP inhibits cell migration by interfering with Rac-induced lamellipodium formation. Chen, L., Zhang, J.J., Huang, X.Y. J. Biol. Chem. (2008) [Pubmed]
  39. Epac, in synergy with cAMP-dependent protein kinase (PKA), is required for cAMP-mediated mitogenesis. Hochbaum, D., Hong, K., Barila, G., Ribeiro-Neto, F., Altschuler, D.L. J. Biol. Chem. (2008) [Pubmed]
  40. Cyclic AMP inhibits JNK activation by CREB-mediated induction of c-FLIP(L) and MKP-1, thereby antagonizing UV-induced apoptosis. Zhang, J., Wang, Q., Zhu, N., Yu, M., Shen, B., Xiang, J., Lin, A. Cell Death Differ. (2008) [Pubmed]
  41. Gonadotropin-stimulated epidermal growth factor receptor expression in human ovarian surface epithelial cells: involvement of cyclic AMP-dependent exchange protein activated by cAMP pathway. Choi, J.H., Chen, C.L., Poon, S.L., Wang, H.S., Leung, P.C. Endocr. Relat. Cancer (2009) [Pubmed]
  42. A competitive inhibitor of phospholipase A2 decreases surfactant phosphatidylcholine degradation by the rat lung. Fisher, A.B., Dodia, C., Chander, A., Jain, M. Biochem. J. (1992) [Pubmed]
  43. Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration. Rozenfeld, C., Martinez, R., Figueiredo, R.T., Bozza, M.T., Lima, F.R., Pires, A.L., Silva, P.M., Bonomo, A., Lannes-Vieira, J., De Souza, W., Moura-Neto, V. Infect. Immun. (2003) [Pubmed]
  44. Increased cyclic GMP content in confluent and serum-restricted heart cell cultures exposed to polyamines. Clô, C., Tantini, B., Pignatti, C., Caldarera, C.M. J. Mol. Cell. Cardiol. (1983) [Pubmed]
  45. Regulation of interphotoreceptor retinoid-binding protein (IRBP) gene expression by cAMP in differentiated retinoblastoma cells. El-Remessy, A.E., Rabie, A.M., El-Shishtawy, M.M., Eissa, L.A., Liou, G.I. Mol. Vis. (2000) [Pubmed]
  46. Differential effects of impaired mitochondrial energy production on the function of mu and delta opioid receptors in neuronal SK-N-SH cells. Raut, A., Iglewski, M., Ratka, A. Neurosci. Lett. (2006) [Pubmed]
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