Phosphodi-esterases

The cAMP formed by adenylyl cyclase (Figure 15.20) does not persist because 5 -phosphodiesterase activity prevalent in cells hydrolyzes cAMP to give 5 -AMP. Caffeine inhibits 5 -phosphodi-esterase activity. Describe the effects on glycogen phosphorylase activity that arise as a consequence of drinking lots of caffeinated coffee. 

Noradrenaline is used to treat shock-like conditions associated with peripheral vasodilatation, e.g. sepsis, systemic inflammatory response syndrome (SIRS), neurogenic shock. The rationale of its use in sepsis and SIRS is to counteract the vasodilatory effects of nitric oxide. Following the surgical removal of phaeochromocytoma and similar tumours, noradrenaline is often given to maintain blood pressure in the initial period. During and after cardiac surgery, it may be used to optimise haemodynamic parameters in combination with other drugs, such as phosphodi-esterase inhibitors. Dose... 

PLATELET cGMP-BINDING, cGMP-SPECIFIC PHOSPHODI-ESTERASE (cGB-PDE, PDE5)... 

Bollen M, Gijsbers R, Ceulemans H, Stalmans W, Stefan C (2000) Nucleotide pyrophosphatases/phosphodi-esterases on the move. Crit Rev Biochem Mol Biol 35 393 32... 

Bowes C, Li T, Danciger M, Baxter LC, Applebury ML, Farber DB. Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodi-esterase. Nature 1990 347 677-680. 

Cyclic AMP- phosphodi- esterase Guinea pig Slight inhibition at high concentrations (229)... 

There continue to be reports of potential prodrugs of biologically-active nucleoside-5 -phosphates. The S-acetyl-2-thioethyl ester 137 of d4T has been prepared, and undergoes esterase hydrolysis in the cell. The same team have also made the analogous derivative of AZT. A series of aromatic aminoacid phosphoramidates of AZT have been described as have bis-ketol AZT monophosphates and 4-acyloxybenzyl bis(nucleosid-5 -yl) phosphates of AZT and ddl. Phosphodi- and tri-esters incorporating both AZT and a metal-com-... 

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