Intestine phosphodiesterase

Direct effects of oximes on the gastrointestinal tract are related entirely to the route of administration—they are seen only after oral administration. Ingestion of tablets of 2-PAM or related salts is often accompanied by transient diarrhea and cramps. The full explanation is not known. In the case of P2S, it has been suggested that a dose of 20 mg/kg inhibits ATPase and therefore produces excess Intestinal fluid and diarrhea. The effect depends on concentration and is reversible. 2-PAM has no effect on cyclic AMP (cAMP), adenylate cyclase, or phosphodiesterase. 

In the small intestine, ribonuclease and deoxyribonuclease I, which are secreted in the pancreatic juice, hydrolyze nucleic acids mainly to oligonucleotides. The oligonucleotides are further hydrolyzed by phosphodiesterases, also secreted by the pancreas, to yield 5 - and 3 -mononucleotides. Most of the mononucleotides are then hydrolyzed to nucleosides by various group-specific nucleotidases or by a variety of nonspecific phosphatases. The resulting nucleosides may be absorbed intact by the intestinal mucosa, or they may un-... 

Most of the enzymes involved in the hydrolysis of dietary DNA and RNA are secreted in the intestine. Thus, ribonucleases are found in the lumen of the small intestine, while the phosphodiesterases and nucleotidases are present in the mucosal cells. 

Papaverin is a stomach and intestine relaxant—a phosphodiesterase (PDE) inhibitor. 

Two diastereoisomers have been identified as radiation induced decomposition products of dC. The synthesis of one of these isomers, (5 5,55,6S)-5, 6-cyclo-5-hydroxy-5,6-dihydro-2 -deoxyuridine (81), and its incorporation into DNA, has been reported The presence of the lesion causes a marked destabilisation of DNA duplexes. The nucleases PI, calf spleen phosphodiesterase and bovine intestinal mucosa phosphodiesterase failed to cleave the lesion, nor was it a substrate for a number of repair enzymes, and it acted as a block to Klenow fragment and Taq polymerases. 

Shikada, K., Yamamoto, A. and Tanaka, S. (1991). Effects of phosphodiesterase inhibitors on vasoactive intestinal peptide-induced relaxation of isolated guinea-pig trachea. Eur. J. Pharmacol. 195, 389-394. 

The incorporation of the 5R and 5S diastereoisomers of the 5-hydroxyhydan-toin (derived from oxidative damage of dC) derivative (89) has been achieved using phosphoramidite chemistry and mild deprotection. Whilst the ODNs containing either diastereoisomer were digested with nuclease Pi, the hydantoin derivatives were resistant to digestion by calf spleen and bovine intestinal mucosa phosphodiesterases. 

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)... 

Venom Phosphodiesterase. A phosphodiesterase from the venom of several species of snakes exhibits extreme specificity with regard to nucleotides. It hydrolyzes only components from a phosphate esterified at a 5 position. Thus, 5 nucleotides are liberated from RNA. The venom diesterase attacks both purine and pyrimidine nucleotides (Fig. 26). This activity was useful in establishing that 3 -5 linkages, rather than 2 -3 linkages, occur in nucleic acids. A similar enzyme occurs in intestines. 

Ribonucleic Acid. A major contribution to the formulation of RNA structure was the demonstration that alkaline hydrolysis of RNA quantitatively liberates about equal amounts of mononucleotide isomers of all four bases 103). Although it was readily established that none of these mononucleotides is the 5 -phosphate isomer, it was not until some years later that Cohn and associates 103) by controlled degradation experiments, and Brown and associates 121) by the synthetic route, established that the products were isomers involving phosphate attachment at positions 2 and 3 of the ribose. Of equal significance was the discovery 161) that hydrolysis of RNA by the enzyme phosphodiesterase (snake venom or intestinal) liberates mononucleotides exclusively of still another type, the 5 -mono-nucleotides. It was thus necessary to establish the mechanisms which could account for one phosphodiester structure in the RNA chain giving rise to three isomers of each mononucleotide. 

Furthermore, incubation of APh-GDP with alkaline phosphatase (intestinal) and phosphodiesterase (snake venom) liberates 4-azidophenol. This leads to an increase in absorption at 303 nm. Incubation with phosphodiesterase alone produces APh-P, and incubation with alkaline phosphatase alone is without effect. 

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