Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Signals that elevate intracellular levels of cyclic adenosine monophosphate (cAMP) are among the factors that control lipopolysaccharide (LPS)-mediated inflammatory mediator production by macrophages. cAMP signaling is also involved in maintaining body functions that are commonly impaired in sepsis, including the endothelial cell barrier function and heart function. Several agents successfully used for sepsis intervention target cAMP signaling, and it was recently shown that liver and lung may be protected from inflammation injury by cAMP-elevating phosphodiesterase inhibitors. Here, we show that LPS attenuates adenylyl cyclase (AC) mRNA levels in liver, lung, heart, spleen and kidney in an animal model of endotoxemia, and in macrophages from liver and lung. In particular, AC5, AC6, AC7 and AC9 mRNA were reduced in most tissues examined and in tissue macrophages. In Kupffer cells, prostaglandin E2-mediated cAMP production was inhibited by LPS treatment. The reduction in AC mRNA by LPS would be expected to lead to a lowered potential for cAMP production in most organs, and in particular, changes in AC6 mRNA may affect endothelial cell barrier function and heart function. In contrast, AC4 mRNA was elevated in heart and lung. The present work indicates a possible mechanism for LPS-mediated alteration of cAMP signaling in vivo.
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PMID:Lipopolysaccharide attenuates mRNA levels of several adenylyl cyclase isoforms in vivo. 1700 68

Regulatory T cells (Treg) are crucial for the suppression of antigen-specific immune responses by activated conventional T cells (Tcon). It has been recently reported that this suppression is mediated by cyclic adenosine monophosphate (cAMP) transported from Treg to Tcon via gap junctions. However, the underlying biochemical mechanisms of cAMP accumulation in activated Treg are still unclear. Here we reported that although non-activated murine Treg and Tcon displayed similar intracellular cAMP amounts, both subpopulations showed distinct expression of enzymes regulating cAMP metabolism. Thus, in Treg, activities of both anabolic (adenylyl cyclase, AC) and catabolic (phosphodiesterase, PDE) enzymes were lower than in Tcon. Furthermore, we demonstrated for the first time the expression of the PDE11 protein in murine Treg and Tcon. Treg activation by IL-2 induced a strong AC7 activation and cAMP accumulation in Treg. In contrast, Tcon showed a significant decrease in the AC7 activity and cAMP amounts under these conditions. Our data suggest that the mechanism of cAMP accumulation in stimulated Treg involves the AC7 activation and provide new insight into the modulation of Treg activities via AC inhibition or stimulation in various pathological processes like tumor and autoimmune diseases.
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PMID:Distinct metabolism of cyclic adenosine monophosphate in regulatory and helper CD4+ T cells. 1993 55