cAMP and cGMP signalling
Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are second messengers for intracellular signal transduction. cAMP and cGMP signalling complex, involving numerous enzymes, receptors and effectors, and is compartmentalized within cells.
G protein-coupled receptors (GPCRs) that are coupled with GαS can stimulate adenylyl cyclase (AC) activity, and thus increase cAMP production from ATP. Several isoforms of AC exist, with different localization and GPCR coupling preferences. cGMP signalling is terminated by cGMP hydrolysis via PDEs, especially PDE4D.
cGMP is produced from GTP by soluble guanylyl cyclase (sGC) and particulate guanylyl cyclase (pGC). The former is activated by nitric oxide (NO), and the latter by natriuretic peptides (NPs). cGMP signalling is terminated by cGMP hydrolysis via PDEs and cGMP export via ABC transporters.
Cyclic nucleotide phosphodiesterases (PDEs) break the phosphodiester bond in cAMP and cGMP, thus ending subcellular signalling by these second messenger molecules. PDEs have different substrate specificities: PDE4, PDE7 and PDE8 are cAMP-selective hydrolases; PDE5, PDE6 and PDE9 are cGMP-selective; and PDE1, PDE2, PDE3, PDE10 and PDE11 can hydrolyse both cAMP and cGMP.
Several PET radioligands targeting PDE10A have been developed, including [11C]IMA107 (Plisson et al., 2014), [11C]Lu AE92686 (Kehler et al., 2014; Yang et al., 2017), [11C]T-773 (Takano et al., 2016), and [18F]JNJ-42259152 (Van Laere et al., 2013).
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Updated at: 2021-12-23
Created at: 2021-12-07
Written by: Vesa Oikonen