The cyclic AMP signaling pathway: Exploring targets for successful drug discovery (Review)

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.

Figure 1

Schematic diagram of second messenger signaling pathways. The figure presents three second messengers involved in three signal transduction pathways, including cAMP-PKA-CREB, NO-cGMP-PKG and IP3-Ca²⁺-PKC. The detection methods, inhibitors and activators of cAMP, PKA, PDE and CREB in the cAMP-PKA-CREB pathway are depicted. cAMP, adenosine 3′,5′-cyclic monophosphate; PKA, protein kinase A; CRE, cAMP response-element; CREB, CRE binding-protein; NO, nitric oxide; cGMP, cyclic guanosine monophosphate; PKG, protein kinase G; IP3, inositol triphosphate; PKC, protein kinase C; PDE, phosphodiesterase; iNOS, inducible nitric oxide synthase; AC, adenylate cyclase; GC, guanylyl cyclase; PLC, phospholipase C; CaM, calmodulin RIA, radioimmunoassay; ELISA, enzyme-linked immunosorbent assay; HPLC-MS, high performance liquid chromatography-mass spectrometry; CTX, cholera toxin; RT-PCR, reverse transcription-quantitative polymerase chain reaction; ChIP, chromatin immunoprecipitation; EMSA, electrophoretic mobility shift assay; SAM, S-adenosylmethionine; IBMX, 3-isobutyl-1-methylxanthine.