Phosphodiesterase kidney

Venom exonuclease [EC 3.1.15.1], also known as venom phosphodiesterase, catalyzes the exonucleolytic cleavage of RNA or DNA (preferring single-stranded substrates) in the 3 to 5 direction to yield 5 -phosphomononucleo-tides. Similar enzymes include hog kidney phosphodiesterase and the Lactobacillus exonuclease. See also specific phosphodiesterase J. A. Gerit (1992) The Enzymes, 3rd ed., 20, 95. 

In man, the volume of distribution of the cyclic nucleotides exceeds the extracellular fluid space [125], and only about 15% of injected labelled cyclic AMP is excreted by the kidney. Extrarenal cyclic nucleotide clearance probably involves hepatic metabolism and/or biliary excretion, but cyclic AMP is also destroyed by renal phosphodiesterase. The isolated perfused rat kidney rapidly removes cyclic AMP from the perfusion medium [126]. 

Olprinone is an inhibitor of phosphodiesterase type III, and has a positive inotropic effect. It is given intravenously and is mostly eliminated by the kidneys. Its pharmacological effects have been reviewed (1). Its major adverse effects are cardiac dysrhythmias and thrombocytopenia, the latter with a reported incidence of 0.43%. 

The alkylxanthines (e.g. the methylxanthines aminophylline and theophylline) are rarely employed as diuretic agents but are commonly used as bronchodilators. Aminophylline is metabolized to its active metabolite theophylline after oral administration and increases cytosolic cyclic adenosine monophosphate (cAMP) by the inhibition of phosphodiesterase, the enzyme responsible for the degradation of cAMP. cAMP is an important intracellular messenger involved in the phosphorylation of cytosolic and membrane-bound proteins however, its effect in the kidneys remains unclear. The diuretic effect of theophylline is modest and appears to be mediated by both an increase in cardiac output, leading to increases in RBF and GFR, and a direct tubular effect, leading to... 

Some information is available on the chemical differences between members of a pair of analogous enzymes. Thus the enzyme that hydrolyses cyclic adenosine monophosphate (cAMP) has been shown to have different molecular composition when specimens from different mammalian tissues were compared (Weiss and Fertel, 1977). Relevantly, pyruvate kinase from healthy liver (L), kidney (K), and muscle (M) of the rat gave inhibitory ratios (L K M) of 1 7.6 6 with 3 -methoxy-ADP, of 1 1.2 7.1 with 8-ethylamino-ADP, and 3 2 1 with methyl-(AT-acetyl-ci) methylaminobutyl)-ADP (Hai, Abo and Hampton, 1982). Similarly, small changes in the substituents inserted into pyrazolo-[1,5-fl]-l, 3,5-triazine 4.53) bring about an inhibition of cAMP phosphodiesterase in different tissues from this list bovine brain, bovine heart, or rabbit lung (Senga etal., 1982). 

Phosphodiesterase 4 inhibitors Nonhuman primates Positive inotropic vasodilating agent Small- and medium-sized arteries of kidneys, stomach, intestine, and mesenteric nodes Segmental vasculitis Vogel et al. (1999)... 

---