scholarly journals Small-Molecule Thyrotropin Receptor Agonist Activates Naturally Occurring Thyrotropin-Insensitive Mutants and Reveals Their Distinct Cyclic Adenosine Monophosphate Signal Persistence

Thyroid ◽  
2011 ◽  
Vol 21 (8) ◽  
pp. 907-912 ◽  
Author(s):  
Michael D. Allen ◽  
Susanne Neumann ◽  
Marvin C. Gershengorn
Keyword(s):  
Small Molecule ◽  
Receptor Agonist ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Thyrotropin Receptor ◽  
Naturally Occurring

scholarly journals Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression

2007 ◽  
Vol 204 (6) ◽  
pp. 1303-1310 ◽  
Author(s):  
Tobias Bopp ◽  
Christian Becker ◽  
Matthias Klein ◽  
Stefan Klein-Heßling ◽  
Alois Palmetshofer ◽  
...  
Keyword(s):  
T Cells ◽  
Gap Junctions ◽  
Gap Junction ◽  
Molecular Mechanisms ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Peripheral Tolerance ◽  
Cell Contact ◽  
Camp Content ◽  
Naturally Occurring

Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact–dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferation and interleukin 2 synthesis in T cells. Upon coactivation with naturally occurring T reg cells the cAMP content of responder T cells is also strongly increased. Furthermore, we demonstrate that naturally occurring T reg cells and conventional T cells communicate via cell contact–dependent gap junction formation. The suppressive activity of naturally occurring T reg cells is abolished by a cAMP antagonist as well as by a gap junction inhibitor, which blocks the cell contact–dependent transfer of cAMP to responder T cells. Accordingly, our results suggest that cAMP is crucial for naturally occurring T reg cell–mediated suppression and traverses membranes via gap junctions. Hence, naturally occurring T reg cells unexpectedly may control the immune regulatory network by a well-known mechanism based on the intercellular transport of cAMP via gap junctions.

scholarly journals Selective small-molecule EPAC activators

2019 ◽  
Vol 47 (5) ◽  
pp. 1415-1427 ◽  
Author(s):  
Urszula Luchowska-Stańska ◽  
David Morgan ◽  
Stephen J. Yarwood ◽  
Graeme Barker
Keyword(s):  
Small Molecule ◽  
Cyclic Nucleotides ◽  
State Of The Art ◽  
Vascular Endothelial Cells ◽  
Vascular Inflammation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Vascular Endothelial ◽  
Secondary Messenger ◽  
Current State

Abstract The cellular signalling enzymes, EPAC1 and EPAC2, have emerged as key intracellular sensors of the secondary messenger cyclic 3′,5′-adenosine monophosphate (cyclic adenosine monophosphate) alongside protein kinase A. Interest has been galvanised in recent years thanks to the emergence of these species as potential targets for new cardiovascular disease therapies, including vascular inflammation and insulin resistance in vascular endothelial cells. We herein summarise the current state-of-the-art in small-molecule EPAC activity modulators, including cyclic nucleotides, sulphonylureas, and N-acylsulphonamides.

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