Cyclic nucleotide phosphodiesterases signaling

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Podzuweit T, Nennstiel P, Muller A (1995) Isozyme selective inhibition of cGMP-stimulated cyclic nucleotide phosphodiesterases by erythro-9-(2-hydroxy-3-nonyl) adenine. Cell Signal 7 733-738... 

Caffeine acts as a stimulant of the central nervous system (CNS) through several proposed mechanisms. The most important seems to be its interference with the ability of the neurotransmitter adenosine to bind to its nerve cell receptor. Also, caffeine inhibits the enzyme cyclic nucleotide phosphodiesterase, which breaks down intracellular cyclic adenosine monophosphate (cAMP), another messenger involved in the transmission of nerve signals from hormones originating outside the central nervous system... 

When the production, and thereby the blood concentration, of adrenaline declines, adrenaline diffuses from the P-receptors. Adenylate cyclase is no longer activated, cAMP production ceases and cytosolic concentrations of cAMP are returned to basal levels by the action of 3, 5 -cyclic nucleotide phosphodiesterase which catalyses the hydrolytic cleavage of cAMP and some other cyclic nucleotides. Protein kinase A reassociates into its inactive form and the inhibition of phosphorylase phosphatase (Figure 10.6) is terminated, signalling the stimulation of the synthetic pathway. 

Adenylyl Cyclases Guanylyl Cyclases Transmembrane Signalling Cyclic Adenosine Monophosphate Cyclic Guanosine Monophosphate Cyclic Nucleotide-gated Channels Phosphodiesterases... 

Cyclic nucleotides are made in response to receptor activation. The receptor activates a G-protein that, in turn, activates adenylyl cyclase to make the cyclic nucleotide. To complete the signaling, the increase in cAMP concentration activates a specific protein kinase (serine/threo-nine), cAMP-dependent protein kinase (A kinase) (Fig. 9-7). To turn off the signaling pathway, the cyclic nucleotides are destroyed by enzymes called phosphodiesterases. These cleave cAMP to AMP. 

Cyclic nucleotides (cAMP and cGMP) are hydrolyzed to destroy the signal. The enzyme that hydrolyzes them is called a phosphodiesterase (more formally, a cAMP or cGMP phosphodiesterase). The signal that activates the synthesis of the cyclic nucleotide will often inhibit the phosphodiesterase. 

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