The Cyclic AMP Signaling Pathway: Exploring Targets for Successful Drug Discovery (Review)

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2016 Apr 2

PMID 27035868

Citations 76

Authors

Kuo Yan

Li-Na Gao

Yuan-Lu Cui

Yi Zhang

Xin Zhou

Affiliations

Soon will be listed here.

Abstract

During development of disease, complex intracellular signaling pathways regulate an intricate series of events, including resistance to external toxins, the secretion of cytokines and the production of pathological phenomena. Adenosine 3',5'-cyclic monophosphate (cAMP) is a nucleotide that acts as a key second messenger in numerous signal transduction pathways. cAMP regulates various cellular functions, including cell growth and differentiation, gene transcription and protein expression. This review aimed to provide an understanding of the effects of the cAMP signaling pathway and the associated factors on disease occurrence and development by examining the information from a new perspective. These novel insights aimed to promote the development of novel therapeutic approaches and aid in the development of new drugs.

Citing Articles

Network pharmacology and metabolomics analysis of Tinospora cordifolia reveals BACE1 and MAOB as potential therapeutic targets for neuroprotection in Alzheimer's disease.

Amrutha S, Abhinand C, Upadhyay S, Parvaje R, Prasad T, Modi P Sci Rep. 2025; 15(1):8103.

PMID: 40057579 PMC: 11890609. DOI: 10.1038/s41598-025-92756-5.

A "Dock-Work" Orange: A Dual-Receptor Biochemical Theory on the Deterrence Induced by Citrusy Aroma on Elephant Traffic Central to a Conservation Effort.

Gunawardana D Bioinform Biol Insights. 2025; 19:11779322251315922.

PMID: 40026377 PMC: 11869256. DOI: 10.1177/11779322251315922.

Mechanistic elucidation of human pancreatic acinar development using single-cell transcriptome analysis on a human iPSC differentiation model.

Mima A, Kimura A, Ito R, Hatano Y, Tsujimoto H, Mae S Sci Rep. 2025; 15(1):4668.

PMID: 39920294 PMC: 11806057. DOI: 10.1038/s41598-025-88690-1.

Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway: a potential therapeutic approach for neurodegenerative diseases.

Deng F, Yang D, Qing L, Chen Y, Zou J, Jia M Neural Regen Res. 2024; 20(11):3095-3112.

PMID: 39589173 PMC: 11881707. DOI: 10.4103/NRR.NRR-D-24-00607.

Repurposing colforsin daropate to treat MYC-driven high-grade serous ovarian carcinomas.

Knarr M, Moon J, Rawat P, DiFeo A, Hoon D, Drapkin R Sci Signal. 2024; 17(863):eado8303.

PMID: 39561220 PMC: 11684408. DOI: 10.1126/scisignal.ado8303.

References

Carey M, Peterson C, Smale S . Chromatin immunoprecipitation (ChIP). Cold Spring Harb Protoc. 2010; 2009(9):pdb.prot5279. DOI: 10.1101/pdb.prot5279. View

Edgar V, Cremaschi G, Sterin-Borda L, Genaro A . Altered expression of autonomic neurotransmitter receptors and proliferative responses in lymphocytes from a chronic mild stress model of depression: effects of fluoxetine. Brain Behav Immun. 2002; 16(4):333-50. DOI: 10.1006/brbi.2001.0632. View

Pinner N, Hamilton L, Hughes A . Roflumilast: a phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease. Clin Ther. 2012; 34(1):56-66. DOI: 10.1016/j.clinthera.2011.12.008. View

Henley J, Huang K, Wang D, Poo M . Calcium mediates bidirectional growth cone turning induced by myelin-associated glycoprotein. Neuron. 2004; 44(6):909-16. PMC: 3121244. DOI: 10.1016/j.neuron.2004.11.030. View

Denninger J, Marletta M . Guanylate cyclase and the .NO/cGMP signaling pathway. Biochim Biophys Acta. 1999; 1411(2-3):334-50. DOI: 10.1016/s0005-2728(99)00024-9. View

Park P, Huang H, McMullen M, Bryan K, Nagy L . Activation of cyclic-AMP response element binding protein contributes to adiponectin-stimulated interleukin-10 expression in RAW 264.7 macrophages. J Leukoc Biol. 2008; 83(5):1258-66. DOI: 10.1189/jlb.0907631. View

Liou S, Hsu J, Lin I, Ho M, Hsu P, Chen L . KMUP-1 suppresses RANKL-induced osteoclastogenesis and prevents ovariectomy-induced bone loss: roles of MAPKs, Akt, NF-κB and calcium/calcineurin/NFATc1 pathways. PLoS One. 2013; 8(7):e69468. PMC: 3723916. DOI: 10.1371/journal.pone.0069468. View

Chang S, Kim D, Ryu G, Ko S, Jeong I, Ahn Y . Exendin-4 inhibits iNOS expression at the protein level in LPS-stimulated Raw264.7 macrophage by the activation of cAMP/PKA pathway. J Cell Biochem. 2012; 114(4):844-53. DOI: 10.1002/jcb.24425. View

Wunder F, Stasch J, Hutter J, Alonso-Alija C, Huser J, Lohrmann E . A cell-based cGMP assay useful for ultra-high-throughput screening and identification of modulators of the nitric oxide/cGMP pathway. Anal Biochem. 2005; 339(1):104-12. DOI: 10.1016/j.ab.2004.12.025. View

10.

Moon E, Lee Y, Choi W, Lee M . Toll-like receptor 4-mediated cAMP production up-regulates B-cell activating factor expression in Raw264.7 macrophages. Exp Cell Res. 2011; 317(17):2447-55. DOI: 10.1016/j.yexcr.2011.07.003. View

11.

Avni D, Philosoph A, Meijler M, Zor T . The ceramide-1-phosphate analogue PCERA-1 modulates tumour necrosis factor-alpha and interleukin-10 production in macrophages via the cAMP-PKA-CREB pathway in a GTP-dependent manner. Immunology. 2009; 129(3):375-85. PMC: 2826682. DOI: 10.1111/j.1365-2567.2009.03188.x. View

12.

Brown K, Lee L, Findlay J, Day J, Baillie G . Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation. FEBS Lett. 2012; 586(11):1631-7. DOI: 10.1016/j.febslet.2012.04.033. View

13.

Metz R, Ziff E . cAMP stimulates the C/EBP-related transcription factor rNFIL-6 to trans-locate to the nucleus and induce c-fos transcription. Genes Dev. 1991; 5(10):1754-66. DOI: 10.1101/gad.5.10.1754. View

14.

Kono Y, Hulsmann S . Presynaptic facilitation of glycinergic mIPSC is reduced in mice lacking α3 glycine receptor subunits. Neuroscience. 2016; 320:1-7. DOI: 10.1016/j.neuroscience.2016.01.063. View

15.

Guseva D, Wirth A, Ponimaskin E . Cellular mechanisms of the 5-HT7 receptor-mediated signaling. Front Behav Neurosci. 2014; 8:306. PMC: 4181333. DOI: 10.3389/fnbeh.2014.00306. View

16.

Dastidar S, Rajagopal D, Ray A . Therapeutic benefit of PDE4 inhibitors in inflammatory diseases. Curr Opin Investig Drugs. 2007; 8(5):364-72. View

17.

Goldsmith M, Avni D, Ernst O, Glucksam Y, Levy-Rimler G, Meijler M . Synergistic IL-10 induction by LPS and the ceramide-1-phosphate analog PCERA-1 is mediated by the cAMP and p38 MAP kinase pathways. Mol Immunol. 2009; 46(10):1979-87. DOI: 10.1016/j.molimm.2009.03.009. View

18.

Moore T, Chetham P, Kelly J, Stevens T . Signal transduction and regulation of lung endothelial cell permeability. Interaction between calcium and cAMP. Am J Physiol. 1998; 275(2):L203-22. DOI: 10.1152/ajplung.1998.275.2.L203. View

19.

Rosethorne E, Nahorski S, Challiss R . Regulation of cyclic AMP response-element binding-protein (CREB) by Gq/11-protein-coupled receptors in human SH-SY5Y neuroblastoma cells. Biochem Pharmacol. 2007; 75(4):942-55. PMC: 2593902. DOI: 10.1016/j.bcp.2007.10.015. View

20.

Landa Jr L, Harbeck M, Kaihara K, Chepurny O, Kitiphongspattana K, Graf O . Interplay of Ca2+ and cAMP signaling in the insulin-secreting MIN6 beta-cell line. J Biol Chem. 2005; 280(35):31294-302. PMC: 3508785. DOI: 10.1074/jbc.M505657200. View