8 bromo cyclic adenosine monophosphate


Summary: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.

Top Publications

  1. Avila E, Díaz L, Barrera D, Halhali A, Mendez I, Gonzalez L, et al. Regulation of Vitamin D hydroxylases gene expression by 1,25-dihydroxyvitamin D3 and cyclic AMP in cultured human syncytiotrophoblasts. J Steroid Biochem Mol Biol. 2007;103:90-6 pubmed
    ..The overall data suggest that calcitriol downregulates CYP27B1 expression via a cAMP-dependent signaling pathway, whereas upregulates 24-hydroxylase gene expression through a VDR-dependent mechanism. ..
  2. Tajima K, Dantes A, Yao Z, Sorokina K, Kotsuji F, Seger R, et al. Down-regulation of steroidogenic response to gonadotropins in human and rat preovulatory granulosa cells involves mitogen-activated protein kinase activation and modulation of DAX-1 and steroidogenic factor-1. J Clin Endocrinol Metab. 2003;88:2288-99 pubmed
    ..Moreover, modulation of DAX-1 and SF-1 intracellular levels in these cells suggests that these transcription factors could be involved in MAPK suppression of StAR expression. ..
  3. Enserink J, Christensen A, de Rooij J, van Triest M, Schwede F, Genieser H, et al. A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat Cell Biol. 2002;4:901-6 pubmed
    ..Moreover, in cell lines in which cAMP activates ERK, inhibition of PKA and Ras, but not Rap1, abolished cAMP-mediated ERK activation. We conclude that cAMP-induced regulation of ERK and activation of Rap1 are independent processes. ..
  4. Thomas J, Gilmour K. The impact of social status on the erythrocyte beta-adrenergic response in rainbow trout, Oncorhynchus mykiss. Comp Biochem Physiol A Mol Integr Physiol. 2006;143:162-72 pubmed
  5. Wilson S, Roche A, Kostetskaia E, Smyth E. Dimerization of the human receptors for prostacyclin and thromboxane facilitates thromboxane receptor-mediated cAMP generation. J Biol Chem. 2004;279:53036-47 pubmed
    ..This represents a previously unknown mechanism by which IP may limit the cellular effects of TP. ..
  6. Puxeddu E, Uhart M, Li C, Ahmad F, Pacheco Rodriguez G, Manganiello V, et al. Interaction of phosphodiesterase 3A with brefeldin A-inhibited guanine nucleotide-exchange proteins BIG1 and BIG2 and effect on ARF1 activity. Proc Natl Acad Sci U S A. 2009;106:6158-63 pubmed publisher
    ..Thus, PDE3A in these BIG1 and BIG2 AKAP complexes may contribute to the regulation of ARF function via limitation of cAMP effects with spatial and temporal specificity. ..
  7. Choi J, Chen C, Poon S, Wang H, Leung P. Gonadotropin-stimulated epidermal growth factor receptor expression in human ovarian surface epithelial cells: involvement of cyclic AMP-dependent exchange protein activated by cAMP pathway. Endocr Relat Cancer. 2009;16:179-88 pubmed publisher
    ..Taken together, these results indicate that the AC/cAMP/Epac signaling pathway may mediate the up-regulation of EGFR by gonadotropins via ERK1/2 and Akt activation. ..
  8. Beetz N, Hein L, Meszaros J, Gilsbach R, Barreto F, Meissner M, et al. Transgenic simulation of human heart failure-like L-type Ca2+-channels: implications for fibrosis and heart rate in mice. Cardiovasc Res. 2009;84:396-406 pubmed publisher
    ..beta(2a)-overexpression by itself did not induce cardiac hypertrophy or contractile dysfunction, but aggravated the development of arrhythmia and fibrosis in Ca(v)1.2-transgenic mice. ..
  9. Aparicio I, Bragado M, Gil M, Garcia Herreros M, Gonzalez Fernandez L, Tapia J, et al. Phosphatidylinositol 3-kinase pathway regulates sperm viability but not capacitation on boar spermatozoa. Mol Reprod Dev. 2007;74:1035-42 pubmed
    ..Finally, in our conditions the PI3-K pathway seems not related with boar sperm capacitation or AR. ..

More Information


  1. Chatelier A, Dahllund L, Eriksson A, Krupp J, Chahine M. Biophysical properties of human Na v1.7 splice variants and their regulation by protein kinase A. J Neurophysiol. 2008;99:2241-50 pubmed publisher
    ..7 can specifically modulate the biophysical properties and cAMP-mediated regulation of this channel. Changing the proportions of these variants may thus influence neuronal excitability and pain sensation. ..
  2. Cifuentes M, Rojas C. Antilipolytic effect of calcium-sensing receptor in human adipocytes. Mol Cell Biochem. 2008;319:17-21 pubmed publisher
  3. Miranda M, McGaugh J. Enhancement of inhibitory avoidance and conditioned taste aversion memory with insular cortex infusions of 8-Br-cAMP: involvement of the basolateral amygdala. Learn Mem. 2004;11:312-7 pubmed
    ..These findings provide additional evidence that the BLA interacts with other brain regions, including sensory cortex, in modulating memory consolidation. ..
  4. Hiroi H, Christenson L, Chang L, Sammel M, Berger S, Strauss J. Temporal and spatial changes in transcription factor binding and histone modifications at the steroidogenic acute regulatory protein (stAR) locus associated with stAR transcription. Mol Endocrinol. 2004;18:791-806 pubmed
    ..Our findings demonstrate that increased StAR transcription can occur in the context of different patterns of transcription factor binding and histone modification. ..
  5. Thangjam G, Agarwal P, Khan I, Verma U, Balapure A, Rao S, et al. Transglutaminase-2 regulation by arecoline in gingival fibroblasts. J Dent Res. 2009;88:170-5 pubmed publisher
    ..Our study provides evidence for TGM-2 overexpression in OSMF and its regulation by arecoline in oral fibroblasts. ..
  6. Sun S, Hsu P, Wu F, Li S, Lu C, Luo C. Thyrostimulin, but not thyroid-stimulating hormone (TSH), acts as a paracrine regulator to activate the TSH receptor in mammalian ovary. J Biol Chem. 2010;285:3758-65 pubmed publisher
    ..Thus, this study demonstrates that oocyte-derived thyrostimulin and granulosa cell-expressed TSHR compose a novel paracrine system in the ovary, where the activity is tightly controlled by gonadotropins. ..
  7. Chang L, Wun A, Hung C, Hsia S, Chiang W, Wang P. Effects of crude adlay hull acetone extract on corticosterone release from rat zona fasciculata-reticularis cells. Naunyn Schmiedebergs Arch Pharmacol. 2006;374:141-52 pubmed
    ..e. 3beta-HSD, 21-hydroxylase, 11beta-hydroxylase, and inhibition of StAR protein expression...
  8. Schroder F, Klein G, Fiedler B, Bastein M, Schnasse N, Hillmer A, et al. Single L-type Ca(2+) channel regulation by cGMP-dependent protein kinase type I in adult cardiomyocytes from PKG I transgenic mice. Cardiovasc Res. 2003;60:268-77 pubmed
    ..Transgenic overexpression of PKG I augments NO/cGMP inhibition but not muscarinic inhibition of single LTCC activity, indicating that PKG I is a downstream target for NO/cGMP, but not the muscarinic receptor in adult cardiac myocytes. ..
  9. Kimura M, Okamoto H, Ogihara M. Activation of mitogen-activated protein kinase by hepatocyte growth factor is stimulated by both alpha1- and beta2-adrenergic agonists in primary cultures of adult rat hepatocytes. J Pharmacol Sci. 2007;103:398-407 pubmed
    ..These results suggest that direct or indirect activation of both PKA and PKC represent a positive regulatory mechanism for stimulating MAPK induction by HGF. ..
  10. Xu G, Van Bockstaele E, Reyes B, Bethea T, Valentino R. Chronic morphine sensitizes the brain norepinephrine system to corticotropin-releasing factor and stress. J Neurosci. 2004;24:8193-7 pubmed
    ..g., hyperarousal, attentional dysfunction), and this may contribute to the maintenance of opiate-seeking behavior. ..
  11. Pesic M, Podolski A, Rakic L, Ruzdijic S. Purine analogs sensitize the multidrug resistant cell line (NCI-H460/R) to doxorubicin and stimulate the cell growth inhibitory effect of verapamil. Invest New Drugs. 2010;28:482-92 pubmed publisher
    ..This feature, together with their ability to reverse MDR, renders the purine analogs (in combination with VER) as potential candidates for improving the clinical activity of existing lung cancer therapeutics. ..
  12. Lo M, Kau M, Wang P. Effect of aging on corticosterone secretion in diestrous rats. J Cell Biochem. 2006;97:351-8 pubmed
    ..In conclusion, aging and PRL play a stimulatory role in the co-regulation of corticosterone secretion. ..
  13. Lambert C. Signaling pathways in ascidian oocyte maturation: the role of cyclic AMP and follicle cells in germinal vesicle breakdown. Dev Growth Differ. 2008;50:181-8 pubmed publisher
    ..Studies with the mitogen-activated protein (MAP) kinase inhibitors U0126 and CI 1040 suggest that MAP kinase is not involved in GVBD. The Cdc25 inhibitor NSC 95397 inhibits GVBD at 200 nm in a reversible manner. ..
  14. Lorenzi I, von Eckardstein A, Cavelier C, Radosavljevic S, Rohrer L. Apolipoprotein A-I but not high-density lipoproteins are internalised by RAW macrophages: roles of ATP-binding cassette transporter A1 and scavenger receptor BI. J Mol Med (Berl). 2008;86:171-83 pubmed
    ..Furthermore, blocking apoA-I uptake inhibits cholesterol efflux to apoA-I but not to HDL. Taken together, these data suggest that apoA-I- but not HDL-mediated cholesterol efflux may involve retroendocytosis...
  15. Nakamoto T, Okada H, Nakajima T, Ikuta A, Yasuda K, Kanzaki H. Progesterone induces the fibulin-1 expression in human endometrial stromal cells. Hum Reprod. 2005;20:1447-55 pubmed
    ..By contrast, beta-estradiol alone did not increase the fibulin-1 mRNA expression. These results suggest that fiblin-1 is an important molecule that mediates progesterone action in human ESC differentiation towards implantation. ..
  16. Dalton G, Smith F, Smith P, Dewey W. Chronic Delta9-tetrahydrocannabinol treatment produces antinociceptive tolerance in mice without altering protein kinase A activity in mouse brain and spinal cord. Biochem Pharmacol. 2005;70:152-60 pubmed
    ..Future work is needed to determine the role of PKA in cannabinoid tolerance in mice. ..
  17. Nishina Y, Takano K, Yasufuku Takano J, Teramoto A, Fujita T. Mechanism of D(2) agonist-induced inhibition of GH secretion from human GH-secreting adenoma cells. Endocr J. 2005;52:775-9 pubmed
  18. Birukova A, Burdette D, Moldobaeva N, Xing J, Fu P, Birukov K. Rac GTPase is a hub for protein kinase A and Epac signaling in endothelial barrier protection by cAMP. Microvasc Res. 2010;79:128-38 pubmed publisher
    ..This study dissected for the first time PKA and Epac pathways of lung EC barrier protection caused by cAMP elevation and identified Rac GTPase as a hub for PKA and Epac signaling leading to enhancement of lung vascular barrier. ..
  19. Bolon M, Ouellette Y, Li F, Tyml K. Abrupt reoxygenation following hypoxia reduces electrical coupling between endothelial cells of wild-type but not connexin40 null mice in oxidant- and PKA-dependent manner. FASEB J. 2005;19:1725-7 pubmed
    ..We propose that abrupt reoxygenation reduces interendothelial electrical coupling via oxidant- and PKA-dependent signaling that targets Cx40. We suggest that this mechanism contributes to compromised arteriolar function after H/R. ..
  20. Kim S, Choi S, Chao W, Volsky D. Transcriptional regulation of human excitatory amino acid transporter 1 (EAAT1): cloning of the EAAT1 promoter and characterization of its basal and inducible activity in human astrocytes. J Neurochem. 2003;87:1485-98 pubmed
    ..Conversely, tumor necrosis factor-alpha reduced both EAAT promoter activity and cellular EAAT1 mRNA expression. These results enable studies of transcriptional regulation of EAAT1 gene at the promoter level. ..
  21. Solntseva E, Bukanova Y, Borisova O. The shift of the reversal potential of glutamate-activated chloride current in molluscan neurons caused by 8-Br-cAMP. Dokl Biol Sci. 2004;399:447-50 pubmed
  22. Llansola M, Sánchez Pérez A, Montoliu C, Felipo V. Modulation of NMDA receptor function by cyclic AMP in cerebellar neurones in culture. J Neurochem. 2004;91:591-9 pubmed
    ..These results indicate that cAMP modulates NMDA receptor in cerebellar neurones and may play a role in NMDA receptor modulation by other receptors. ..
  23. Miyoshi K, Kawakami N, Horio S, Fukui H. Inhibition of histamine H1 receptor downregulation by KT5823, a protein kinase G inhibitor. Methods Find Exp Clin Pharmacol. 2003;25:343-7 pubmed
    ..Similarly, histamine-induced downregulation of H(1)R was unaffected by either H-89, an inhibitor of protein kinase A, or 8-Br-cAMP, a membrane-permeable analogue of cAMP. ..
  24. Avila E, Díaz L, Halhali A, Larrea F. Regulation of 25-hydroxyvitamin D3 1alpha-hydroxylase, 1,25-dihydroxyvitamin D3 24-hydroxylase and vitamin D receptor gene expression by 8-bromo cyclic AMP in cultured human syncytiotrophoblast cells. J Steroid Biochem Mol Biol. 2004;89-90:115-9 pubmed
    ..The data also suggest a tissue-dependant differential regulation of CYP27B1 gene expression by cAMP. ..
  25. Takami Y, Yamamoto I, Tsubouchi H, Gohda E. Modulation of hepatocyte growth factor induction in human skin fibroblasts by retinoic acid. Biochim Biophys Acta. 2005;1743:49-56 pubmed
    ..These results suggest that ATRA augments the induction of HGF production caused by increased intracellular cAMP. ..
  26. Takada M, Fujimaki K, Hokari S. Vasotocin has the potential to inhibit basolateral Na(+)/K (+)-pump current across isolated skin of tree frog in vitro, via its V(2)-type receptor/cAMP pathway. J Comp Physiol B. 2008;178:957-62 pubmed publisher
    ..To judge from these in vitro experiments, AVT has the potential to inhibit the basolateral Na(+)/K(+)-pump current via the V(2)-type receptor/cAMP pathway in the skin of the tree frog. ..
  27. Citterio C, Jones H, Pacheco Rodriguez G, Islam A, Moss J, Vaughan M. Effect of protein kinase A on accumulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) in HepG2 cell nuclei. Proc Natl Acad Sci U S A. 2006;103:2683-8 pubmed
    ..Thus, two more critical elements of BIG1 molecular structure were identified, as well as the potential function of microtubules in a novel PKA effect on BIG1 translocation. ..
  28. Haag S, Warnken M, Juergens U, Racke K. Role of Epac1 in mediating anti-proliferative effects of prostanoid EP(2) receptors and cAMP in human lung fibroblasts. Naunyn Schmiedebergs Arch Pharmacol. 2008;378:617-30 pubmed publisher
    ..In conclusion, Epac1 rather than the classic cAMP effector PKA is a crucial element in the signal transduction pathway mediating anti-proliferative effects of EP(2) receptor activation. ..
  29. Geng W, Hill K, Zerwekh J, Kohler T, Muller R, Moe O. Inhibition of osteoclast formation and function by bicarbonate: role of soluble adenylyl cyclase. J Cell Physiol. 2009;220:332-40 pubmed publisher
    ..This HCO(3)(-) effect on BV/TV was blocked by 2-hydroxyestradiol. In summary, sAC mediates the inhibition of osteoclast function by HCO(3)(-), by acting as a HCO(3)(-) sensor...
  30. Liu H, Enyeart J, Enyeart J. ACTH induces Cav3.2 current and mRNA by cAMP-dependent and cAMP-independent mechanisms. J Biol Chem. 2010;285:20040-50 pubmed publisher
    ..Surprisingly, chlorophenylthio-cAMP analogs stimulate the expression of Ca(v)3.2 current indirectly through metabolites. ACTH and the metabolites may induce Ca(v)3.2 expression by the same, unidentified mechanism...
  31. YaDeau J, Morelli C, Billingsley J. Ketamine stimulates secretion of beta-endorphin from a mouse pituitary cell line. Reg Anesth Pain Med. 2003;28:12-6 pubmed
    ..This suggests that the prolonged analgesia observed in some clinical situations with ketamine could be in part caused by increased release of an endogenous opioid. ..
  32. Lu Z, Kolodecik T, Karne S, Nyce M, Gorelick F. Effect of ligands that increase cAMP on caerulein-induced zymogen activation in pancreatic acini. Am J Physiol Gastrointest Liver Physiol. 2003;285:G822-8 pubmed
    ..The cAMP antagonist Rp-8-Br-cAMP inhibited these sensitizing effects. These findings suggest that ligands that increase acinar cell cAMP levels can sensitize the acinar cell to the effects of CCK-induced zymogen activation. ..
  33. Li S, Doss J, Hardee E, Quock R. Involvement of cyclic GMP-dependent protein kinase in nitrous oxide-induced anxiolytic-like behavior in the mouse light/dark exploration test. Brain Res. 2005;1038:113-7 pubmed
    ..These findings implicate PKG in the mediation or modulation of the anxiolytic-like behavioral response to N2O. ..
  34. Bodnar R, Yates C, Wells A. IP-10 blocks vascular endothelial growth factor-induced endothelial cell motility and tube formation via inhibition of calpain. Circ Res. 2006;98:617-25 pubmed
    ..This provides a means by which late wound repair signals limit the angiogenesis driven early in the wound response process. ..
  35. Nevzorova J, Evans B, Bengtsson T, Summers R. Multiple signalling pathways involved in beta2-adrenoceptor-mediated glucose uptake in rat skeletal muscle cells. Br J Pharmacol. 2006;147:446-54 pubmed
    ..PKA appears to negatively regulate beta2-AR-mediated GU. ..
  36. Colonna C, Podesta E. ACTH-induced caveolin-1 tyrosine phosphorylation is related to podosome assembly in Y1 adrenal cells. Exp Cell Res. 2005;304:432-42 pubmed
  37. Waleh N, Kajino H, Marrache A, Ginzinger D, Roman C, Seidner S, et al. Prostaglandin E2--mediated relaxation of the ductus arteriosus: effects of gestational age on g protein-coupled receptor expression, signaling, and vasomotor control. Circulation. 2004;110:2326-32 pubmed publisher
  38. Flecke C, Nolte A, Stengl M. Perfusion with cAMP analogue affects pheromone-sensitive trichoid sensilla of the hawkmoth Manduca sexta in a time-dependent manner. J Exp Biol. 2010;213:842-52 pubmed publisher
  39. Martin L, Tremblay J. Glucocorticoids antagonize cAMP-induced Star transcription in Leydig cells through the orphan nuclear receptor NR4A1. J Mol Endocrinol. 2008;41:165-75 pubmed publisher
    ..Thus, our data provide new molecular insights into the stress-mediated suppression of testosterone production in testicular Leydig cells. ..
  40. Clarke D, Belvisi M, Catley M, Yacoub M, Newton R, Giembycz M. Identification in human airways smooth muscle cells of the prostanoid receptor and signalling pathway through which PGE2 inhibits the release of GM-CSF. Br J Pharmacol. 2004;141:1141-50 pubmed
    ..In addition, the data illustrate that caution should be exercised when using H-89 in studies designed to assess the role of PKA in biological processes. ..
  41. Mead J, Hughes T, Irvine S, Singh N, Ramji D. Interferon-gamma stimulates the expression of the inducible cAMP early repressor in macrophages through the activation of casein kinase 2. A potentially novel pathway for interferon-gamma-mediated inhibition of gene transcription. J Biol Chem. 2003;278:17741-51 pubmed
  42. Denis M, Bissonnette R, Haidar B, Krimbou L, Bouvier M, Genest J. Expression, regulation, and activity of ABCA1 in human cell lines. Mol Genet Metab. 2003;78:265-74 pubmed
    ..Taken together, these results demonstrate that: (1) ABCA1 expression varies among tissues, and (2) cholesterol conversion to hydroxycholesterol is an important mechanism for the maintenance of cholesterol homeostasis in fibroblasts...
  43. Qiao S, Okret S, Jondal M. Thymocyte-synthesized glucocorticoids play a role in thymocyte homeostasis and are down-regulated by adrenocorticotropic hormone. Endocrinology. 2009;150:4163-9 pubmed publisher
    ..We conclude that thymocyte-produced GCs are important for the homeostasis of adult mouse thymocytes and that high ACTH level, in contrast to stimulating GC synthesis in the adrenal glands, has the opposite effect in thymocytes. ..
  44. Zholos A, Tsytsyura Y, Gordienko D, Tsvilovskyy V, Bolton T. Phospholipase C, but not InsP3 or DAG, -dependent activation of the muscarinic receptor-operated cation current in guinea-pig ileal smooth muscle cells. Br J Pharmacol. 2004;141:23-36 pubmed
  45. Yan L, Zhang Q, Scholz P, Weiss H. Cyclic GMP protein kinase activity is reduced in thyroxine-induced hypertrophic cardiac myocytes. Clin Exp Pharmacol Physiol. 2003;30:943-50 pubmed
  46. Keller J, McClellan Green P. Effects of organochlorine compounds on cytochrome P450 aromatase activity in an immortal sea turtle cell line. Mar Environ Res. 2004;58:347-51 pubmed
    ..Based on these results, this in vitro model can be useful in examining the endocrine effects of EACs in sea turtles. ..
  47. Branski P, Palucha A, Szewczyk B, Wieronska J, Pilc A, Nowak G. Antidepressant-like activity of 8-Br-cAMP, a PKA activator, in the forced swim test. J Neural Transm (Vienna). 2008;115:829-30 pubmed publisher
    ..This effect was antagonized by co-treatment with selective PKA inhibitor Rp-cAMPS. This is the first demonstration of the antidepressant-like activity of the PKA activator. ..
  48. De Petrocellis L, Starowicz K, Moriello A, Vivese M, Orlando P, Di Marzo V. Regulation of transient receptor potential channels of melastatin type 8 (TRPM8): effect of cAMP, cannabinoid CB(1) receptors and endovanilloids. Exp Cell Res. 2007;313:1911-20 pubmed
  49. Nakajima S, Tanaka T, Umesaki N, Ishiko O. Leukemia inhibitory factor regulates cell survival of normal human endometrial stromal cells. Int J Mol Med. 2003;11:353-6 pubmed
  50. Liu L, Yang T, Bruno M, Andersen O, Simon S. Voltage-gated ion channels in nociceptors: modulation by cGMP. J Neurophysiol. 2004;92:2323-32 pubmed
    ..This pathway may be a target for efforts to produce selective analgesics. ..
  51. Babiker F, De Windt L, van Eickels M, Thijssen V, Bronsaer R, Grohe C, et al. 17beta-estradiol antagonizes cardiomyocyte hypertrophy by autocrine/paracrine stimulation of a guanylyl cyclase A receptor-cyclic guanosine monophosphate-dependent protein kinase pathway. Circulation. 2004;109:269-76 pubmed
    ..KT-5823 not only reversed the antihypertrophic properties of E2, ANF, or 8-bromo-cGMP, but also evoked potentiation of hypertrophy. E2-mediated induction of ANF in cardiac hypertrophy contributes to its antagonistic effects in LVH. ..
  52. Weissinger E, Oettrich K, Evans C, Genieser H, Schwede F, Dangers M, et al. Activation of protein kinase A (PKA) by 8-Cl-cAMP as a novel approach for antileukaemic therapy. Br J Cancer. 2004;91:186-92 pubmed
    ..In summary, our results indicate that 8-Cl-cAMP could be useful to purge malignant cells from the bone marrow of patients with CML and certain other forms of leukaemias. ..
  53. Benjamins J, Nedelkoska L. Cyclic GMP-dependent pathways protect differentiated oligodendrocytes from multiple types of injury. Neurochem Res. 2007;32:321-9 pubmed
    ..The cAMP analog exhibited little or no protection against kainate or high levels of NO. Thus cGK signaling is more effective than protein kinase A or phosphodiesterase 3 signaling in preventing OL death. ..