Cyclic nucleotides adenylyl cyclases

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

PDE1C2 and PDE4A are expressed. PDE1C2 is found in the cilia of the epithelium, where it colocalizes with adenylyl cyclase. PDE4A is found throughout the epithelial layer, but not in cilia. Therefore, as in the kidney mesangial cells, different PDEs must be working on different cyclic nucleotide pools. More recently, substantial data has been developed for compartmenta-tion of cAMP and PDEs in cardiac myocytes. 

Cyclic nucleotide metabolism cyclic nucleotide Phosphodiesterase Adenylyl cyclase... 

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. 

Concentration of cAMP is controlled primarily by two means, namely via new synthesis by adenylyl cyclase and degradation by phosphodiesterases (review Houslay Milligan, 1997). In addition to adenylyl cyclase, the activity of which is subject to diverse regulation (see 5.6.1), the cAMP phosphodiesterases are also an important point of attack for control of the cAMP level. There are phosphodiesterases regulated by Ca Vcahnoduhn and by protein phosphorylation. More than 10 different isoforms of phosphodiesterase are known, which vary in their cyclic nucleotide specificity and in their regulation. 

Dipyridamole (Persantine) is a vasodilator that, in combination with warfarin, inhibits embolization from prosthetic heart valves and, in combination with aspirin, reduces thrombosis in patients with thrombotic diseases. Dipyridamole by itself has little or no benefit in fact, in trials where a regimen of dipyridamole plus aspirin was compared with aspirin alone, dipyridamole provided no additional beneficial effect. Dipyridamole interferes with platelet function by increasing the cellular concentration of adenosine 3, 5 -monophosphate (cyclic AMP). This effect is mediated by inhibition of cyclic nucleotide phosphodiesterase and by blockade of uptake of adenosine, which acts at A2 receptors for adenosine to stimulate platelet adenylyl cyclase. The only current recommended use of dipyridamole is for primary prophylaxis of thromboemboli in patients with prosthetic heart valves the drug is given in combination with warfarin. 

The cyclic nucleotides adenosine 3, 5 -cyclic monophosphate (cyclic AMP (cAMP)) and guanosine 3, 5 -cyc.lic monophosphate (cyclic GMP (c.GMP)) are second messengers generated by adenylyl (adenylate) cyclase (AC) and guanylyl (guanylate) cyclase (GC), respectively, in response to receptor occupation by particular primary messengers , that is,... 

Cyclic nucleotide regulated protein kinase family = Adenylyl cyclases = A-kinase anchor proteins = Atypical PKCs = Atrial natriuretic peptide = Adenosine 5 -triphosphate = Brain natriuretic peptide = Ca Vcalmodulin-dependent kinases = Cyclin-dependent kinases = Ca -dependent protein kinase = Casein kinase I = Casein kinase II = Dcd-like kinase... 

Dipyridamole interferes with platelet function by increasing the cellular concentration of cyclic AMP. This effect is mediated by inhibition of cyclic nucleotide PDFs and/or by blockade of uptake of adenosine, which acts at adenosine receptors to stimulate platelet adenylyl cyclase. The only... 

Adenylyl-cyclase/cAMP system. Sutherland s studies revealed that the intracellular messenger cyclic 3, 5 -adenosine monophosphate (cyclic-AMP) is a nucleotide synthesized within the cell from ATP by the action of adenylyl-cyclase. Receptors linked to Gs activate adenylyl-... 

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