Inhibition of purine nucleoside phosphorylase activity and of T-cell function with allopurinol-riboside.
Allopurinol-riboside competitively inhibits the action of purine nucleoside phosphorylase on inosine in vitro with a Ki of 277 mumol. After simple incubation of allopurinol-riboside with PNP, allopurinol was not formed. Lymphocyte blastogensis induced by PHA and Con A was significantly suppressed by allopurinol-riboside in a concentration-dependent manner. When LPS was used as a mitogen, the inhibition of allopurinol-riboside on lymphocyte proliferation was less marked. Humoral immunity was not suppressed by allopurinol-riboside. In contrast, cellular immunity was significantly suppressed by allopurinol-riboside in vivo. These results suggested that allopurinol-riboside is a drug which produces a model of PNP deficiency, and that it may be a useful inhibitor of cellular immunity.
D000493:Allopurinol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D012263:Ribonucleosides / Q000378:metabolism / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
D010835:Phytohemagglutinins; D012263:Ribonucleosides; D003208:Concanavalin A; D000493:Allopurinol; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; C021958:allopurinol riboside