An RIA is a radionuclide-labeled immune analysis method. Developed in the 1970's, a radioimmunoassay (RIA) ( 22) is used to detect the concentration of cAMP. Therefore, detecting the level of cAMP is important in the investigation of medically relevant signal transduction pathways.Īn immunochemical assay is a fast and effective method for detecting cAMP in the field of biomedical research. With functions including the regulation of neurotransmitter synthesis ( 19), regulation of membrane protein activity, participation in ganglion synaptic transmission ( 20) and regulation of transcription factors in eukaryotic cells ( 21), cAMP may be involved in the prevention and treatment of various diseases. The present review discusses the methods used to detect the cAMP signaling pathway, as well as the diseases associated with the pathway.ĬAMP, as an important messenger involved in the regulation of metabolism and biological functions in cells, transfers information regarding cellular status. Due to the importance and varied functions of the cAMP signaling pathway, Gloerich and Bos ( 12) and Nakajima et al ( 13) studied the underlying mechanisms in detail. All of the conditions and diseases mentioned above involve the cAMP signaling pathway and its branch pathway. Second messenger pathways are associated with numerous conditions and diseases, including inflammation ( 6, 7), cancer ( 8, 9), myocardial atrophy ( 2), asynodia ( 10) and depression ( 11). Phosphodiesterases (PDEs) are an enzyme superfamily that have been demonstrated to catalyze the hydrolysis of intracellular second messenger molecules, including cAMP and cGMP therefore, the inactivation of PDE will indirectly increase the level of cAMP in cells ( 5). Extracellular signals activate the transcription of a variety of target genes via alterations in CREB phosphorylation, thereby, resulting in multiple physiological functions ( 4). The phosphorylation of the cAMP response-element binding-protein (CREB), a transcription factor, is important in the regulation of gene transcription ( 3). Subsequently, specific proteins are phosphorylated by PKA ( 2) to evoke cellular reactions. 1.Īdenylate cyclase (AC) converts adenosine triphosphate (ATP) into cAMP, which stimulates cAMP-dependent protein kinase A (PKA). Signal response factors associated with cAMP are discussed below and the current understanding of the cAMP signaling pathway is presented in Fig. This review focuses primarily on reviewing cAMP, an important second messenger, and the associated cell signal transduction pathway. It has been identified that numerous signaling pathways are triggered by second messengers including cAMP, diacylglycerol, inositol triphosphate (IP 3), cGMP and Ca 2+. The degradation of these second messengers leads to signal termination. Second messengers convert and amplify extracellular signals by activating protein kinases that serve physiological roles or by acting on intracellular ligand-gated channels to alter the membrane potential. 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. The detection methods, inhibitors and activators of cAMP, PKA, PDE and CREB in the cAMP-PKA-CREB pathway are depicted. The figure presents three second messengers involved in three signal transduction pathways, including cAMP-PKA-CREB, NO-cGMP-PKG and IP3-Ca 2+-PKC. Schematic diagram of second messenger signaling pathways.
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