cAMP Full Form

Cells must detect and integrate many extracellular and intracellular signals to change their activities. Second, messengers are the starting points for intracellular signal transduction cascades that carry messages from cellular messengers that rely on external signalling molecules. Second, messengers boost the intensity of the original initial signal in this way. The first to be found was the intracellular second messenger of extracellular ligand action, cyclic adenosine monophosphate (cAMP). cAMP modulates pro- and anti-inflammatory activity in the immune system: medications that raise intracellular cAMP levels lower pro-inflammatory mediator synthesis while increasing anti-inflammatory factor production in various immune cells.

cAMP Full Form

cAMP stands for the cyclic adenosine monophosphate. The first intracellular second messenger of extracellular ligand action, cyclic adenosine monophosphate, was discovered in 1957 and is recognized as a universal regulator of metabolism and gene expression in all living forms. Adenylate cyclases (AC) are enzymes that catalyze the synthesis of cAMP from ATP. AC has nine membrane-bound isoforms and one soluble isoform in invertebrates. The location and developmental expression of AC varies, and their control is complicated and isozyme specific. A subfamily of phosphodiesterases (PDE) that breakdown intracellular cyclic nucleotides regulate cAMP homeostasis in addition to AC expression and activity. PDE enzymes are classified into 11 families based on their structure, selectivity for cyclic nucleotides, and regulation.

Certain PDEs respond to cAMP by increasing their activity, while cAMP increases the manufacture of additional PDE mRNA, resulting in a feedback loop between cAMP levels and PDE activity. Some PDE families are cAMP-specific, while others are cyclic guanosine monophosphate (cGMP)-specific, adding to the pathway’s complexity. Additional families hydrolyze both cAMP and cGMP, resulting in cross-regulation of both paths, which has crucial implications for the efficacy of cyclic nucleotide metabolism-targeting drugs.

Anatomy of the System

When an external first messenger (neurotransmitter, hormone, chemokine, lipid mediator, or drug) binds to a seven-transmembrane–spanning G protein-coupled receptor (GPCR) connected to a stimulatory G protein subunit (Gs), cAMP is generated. Ligand binding causes the Gs protein to exchange GDP for GTP, resulting in its separation from the component complex. The free Gs subunit stimulates the enzyme adenylyl cyclase (AC) to catalyse the cyclisation of ATP to create cAMP and pyrophosphate. Epinephrine and norepinephrine, histamine, serotonin, and some COX-derived prostaglandins E2 and I2 are only a few well-known Gs-coupled GPCR ligands. On the other hand, Gi subunits limit AC and cAMP synthesis; Gi-coupled GPCR ligands include chemokines CCR1–10 and CXCR1–6, as well as leukotrienes B4, C4, and D4.

There are now ten AC isoforms expressed differently in different cell types. Not only does AC influence intracellular cAMP levels, but so does the enzyme phosphodiesterase (PDE). By decomposing intracellular cAMP, PDEs block cAMP signalling. There are 11 different PDE gene families, each with tissue-specific expression. Furthermore, because both ACs and PDEs may be found in distinct spatial compartments within the cell, the ephemeral presence of cAMP can be controlled at the subcellular level.

Functions: cAMP and Phagocyte Effector

Intracellular cAMP levels suppress innate immune functions of monocytes, macrophages, and neutrophils (PMNs) (collectively referred to as phagocytes) by modulating three essential effector functions of these cells:

• Inflammatory mediator production (e.g., cytokine, chemokine, and lipids)
• Phagocytosis
• Intracellular killing of ingested pathogens

Dendritic cells, essential cellular adaptors of innate and acquired immunity, have a host defence function that is very vulnerable to cAMP modulation, although this is not explored here. While many natural immune defences mediators’ function through Gαi-coupled receptors, the extent to which their immunostimulatory actions are dependent on intracellular cAMP decreases and cAMP effector pathway degradation is unknown.

Utilization By Microbes of the Host Camp System

The discovery that some pathogenic bacteria have evolved methods to exploit host cell cAMP signalling as a virulence factor emphasises the relevance of cAMP as a negative regulator of antimicrobial responses. Microbial infections can raise host cell intracellular cAMP synthesis directly or indirectly by eliciting host autocrine and paracrine mediators that promote cAMP production subsequently. Pathogens gain an advantage in establishing infection by utilising cAMP to inhibit host cell phagocytosis, intracellular death, and inflammatory mediator production.

Bordetella pertussis (the bacteria that causes whooping cough) is a remarkable illustration of how a bacterium may disrupt innate immune systems simply by overpowering the cAMP regulatory mechanism of host cells. The well-known pertussis toxin (PT) and the less well-known AC toxin, CyaA, are produced by B. pertussis. although in different ways, both PT and CyaA toxins stimulate cAMP in host cells. The ADP ribosylation of the inhibitory Gi subunit by B. pertussis PT increases intracellular cAMP levels in target cells. PT inhibits phagocytosis and ROI formation in macrophages and PMN migration to the lungs during infection. CyaA is a pore-forming toxin with an AC motif activated by eukaryotic calmodulin and catalyses the uncontrolled conversion of cellular ATP to cAMP. CyaA suppresses the host defensive activities of myeloid phagocytes such AMs and PMNs in vivo, according to research. Superoxide generation, chemotaxis, cytokine synthesis, and phagocytosis are all affected by CyaA. In addition to CyaA, three additional calmodulin-dependent AC toxins have been discovered: Bacillus anthracite edoema factor, Pseudomonas aeruginosa’s ExoY, and Yersinia pestis’ AC.

Conclusion

Increased cAMP inhibits inflammatory mediator production, phagocytosis, and microbial death, suggesting that changes in cAMP levels significantly impact phagocyte innate immune responses. cAMP’s immunosuppressive effects are widespread, affecting many inherent immune cell types and their interactions with many microbes. The impact of host-derived molecules, pathogen-derived molecules, and pharmaceutical agents all result in cAMP disturbances, which are many and frequent. The molecular underpinnings and clinical implications of such cAMP alterations on innate immune activity are unknown. However, gaining a greater knowledge of the cAMP axis is expected to lead to new insights into the control of innate immunity, which might lead to therapeutic benefits.