Search PubMed⌕ Search

Biomedical subjects

R E Parks

Publications and source records attributed to R E Parks.

At least 55 records · Page 3Linked to original sources
PubMed1982

Inhibition of human and rat platelet aggregation by extracts of Mo-er (Auricularia auricula).

Hot water extracts of Mo-er (1 gm by 15 ml of water), an oriental food (Auricularia auricula), inhibit strongly both human and rat platelet ADP-induced aggregation. HPLC analysis of two varieties of Mo-er, A. auricula and A. polytricha (a black tree fungus), shows that they contain adenosine (Ado), 133 and 154 micrograms per gram of dry fungus, respectively. The inhibition of ADP-induced platelet aggregation by Mo-er extracts and by Ado was compared. Mo-er extracts caused a more rapid onset and a longer duration of inhibition that produced by equivalent amounts of Ado. Furthermore, Mo-er extract treated with adenosine deaminase to degrade the Ado retained the capacity to inhibit platelet aggregation. The inhibitory effects of Mo-er extracts of ADP-induced human platelet aggregation are greatly potentiated by the inhibitors of cyclic AMP phosphodiesterase such as oxagrelate (phthalazinol) and papaverine. The inhibition of platelet aggregation is only partially blocked by 2',5'-dideoxy-adenosine (DDA), an inhibitor of platelet adenylate cyclase and 5'-deoxy, 5'-methylthioadenosine (MTA), an antagonist of ADO receptors. ADP-induced rat platelet aggregation is strongly inhibited by Mo-er extracts, but not by Ado. This inhibition is not reversed by either DDA or MTA. These findings indicate that Mo-er extracts contain an agent (or agents) in addition to Ado, that blocks platelet aggregation by a mechanism that does not involve the platelet cyclic AMP system.

Adenosine↗
PubMed1982

Biochemical pharmacology and toxicology of 8-azaadenosine alone and in combination with 2'-deoxycoformycin (pentostatin).

The toxicology and metabolism of 8-azaadenosine (8-azaAdo) were examined both as a single agent and in combination with the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF). The LD10 (mice) for 8-azaAdo alone on a once daily for 5 days (q.d. x 5) schedule was 30 mg . kg-1 . day-1. When the animals were pretreated with 0.1 mg . kg-1 . day-1 of dCF, the LD10 dose was reduced to 10 mg . kg-1 . day-1 x 5. The major organ toxicity seen was hepatic. Bone marrow cellularity was only slightly altered at the LD10 dose. 8-AzaAdo nucleotides were detected in the livers of treated mice as determined by high performance liquid chromatography. Further, after 2 hr of incubation, isolated rat hepatocytes accumulated 8-azaATP to levels of 2.2 mumoles/g of cells with 8-azaAdo (1 mM) alone and to 4.3 mumoles/g of cells when 8-azaAdo was used in combination with dCF (1 microgram/ml). ATP levels decreased to below the limits of detection after 2 hr in cells treated with the combination. The replacement of cellular ATP by 8-azaATP may provide an explanation for the hepatotoxicity observed in the murine toxicology studies.

Adenosine↗
PubMed1982

C(2')-substituted purine nucleoside analogs. Interactions with adenosine deaminase and purine nucleoside phosphorylase and formation of analog nucleotides.

Four C(2')-substituted 2'-deoxyadenosines were examined as substrates for human erythrocytic adenosine deaminase and for formation of intracellular nucleotide analogs in human erythrocytes, lymphocytes and murine Sarcoma 180 cells: 9-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)adenine, 9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)adenine, 9-(2'-azido-2'-deoxy-beta-D-ribofuranosyl)adenine (2'-N3-riboA) and 9-(2-azido-2'-deoxy-beta-D-arabinofuranosyl)adenine. All four adenosine analogs were substrates of human erythrocytic adenosine deaminase, but the corresponding inosine analogs (synthesized by the adenosine deaminase reaction) were highly resistant to cleavage by human erythrocytic purine nucleoside phosphorylase. Only 9-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)hypoxanthine underwent very slow phosphorolysis, and no inhibition of inosine phosphorolysis was detected when a 30 microM concentration of any studied inosine analog was added to a reaction mixture containing 30 microM inosine (the Km concentration). Kinetic parameters were determined for the deamination of the adenosine analogs. The greatest affinity for adenosine deaminase was found with 2'-N3-ribo A (Ki = 2 microM), but the reaction velocity was highest with the F-substituted analogs. All four adenosine analogs formed triphosphate nucleotides after incubation with human erythrocytes, murine Sarcoma 180 cells, or human lymphocytes (tested only with the F analogs) in the presence of deoxycoformycin.

Adenosine Deaminase↗
PubMed1981

Crystallization and preliminary X-ray investigation of human erythrocytic purine nucleoside phosphorylase.

Crystals of human erythrocytic purine nucleoside phosphorylase have been grown from solutions of ammonium sulfate. The crystals are trigonal, space group R32; the hexagonal axes are a = 143.8(2) and c = 165.1(2) A. The crystals are moderately stable to x-rays and diffract beyond 3.0 A resolution. The experimental density of the crystals indicates that the molecular weight of the protein is 94,000. The three subunits are not related by crystallographic symmetry.

Crystallization↗
PubMed1980

Human erythrocytic purine nucleoside phosphorylase: reaction with sugar-modified nucleoside substrates.

The kinetic parameters (Km and Vmax) of sugar-modified analogues of inosine and guanosine have been determined with human erythrocytic purine nucleoside phosphorylase (PNP). Steric alterations at the 2' and 3' positions greatly lessened or abolished substrate activity. However, the 5'-deoxy- and 2',5'-dideoxy-beta-D-ribofuranosyl and the alpha-L-lyxosyl analogues were good substrates, indicating that the 5'-hydroxyl and the orientation of the 5'-hydroxy-methyl group are not important for binding. The sugar phosphate analogue, 5-deoxyribose 1-phosphate, was synthesized from 5'-deoxyinosine with immobilized PNP, and its presence was verified by using it in the enzymic synthesis of 5'-deoxyguanosine. The adenosine versions of the 5'-modified analogues were also found to react with adenosine deaminase, albeit at less than 1% of Vmax.

Erythrocytes↗