Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the actions of a novel xanthine derivative, propentofylline (HWA 285), that has been shown to protect against ischemic brain damage in rats and gerbils, on adenosine receptors (A1 and A2), and on adenosine transporters using several techniques, cells and tissues. Propentofylline and its hydroxylated metabolite A 72 0287 were about 20 times less potent than theophylline in displacing A1-agonist binding to membranes from rat cortex, and A1-antagonist binding to whole DDT, MF-2 smooth muscle cells. A1-agonist binding to adenosine A1-receptors in several brain structures was inhibited in a concentration-dependent manner by A 72 0287 and propentofylline as judged by quantitative autoradiography (IC50-values 300-600 microM in eg striatum and in cortex layer IV). In two functional assays, A1-receptor mediated effects were blocked by propentofylline. A1-receptor-mediated inhibition of cyclic AMP accumulation was virtually abolished by 100 microM propentofylline. The A1-receptor-mediated inhibition of evoked acetylcholine release was also reduced by propentofylline, but in this case the effect is not due exclusively to adenosine receptor antagonism but also to another action since the presynaptic inhibitory effect of carbachol was also inhibited. Adenosine A2-receptors were also antagonized by propentofylline as judged by a concentration-dependent antagonism of A2-agonist-induced cAMP accumulation in human T-leukemia cells (possessing putative A2b-receptors; pA2-value 180 microM compared to 0.26 microM for 8-cpt), and in PC-12 cells (possessing putative A2a-receptors, Ki-value 365 microM). Finally, adenosine transporters were affected by propentofylline and A 72 0287. Thus, [3H]-nitrobenzylthioinosine-binding to guinea-pig cardiac membranes was blocked by propentofylline or A 72 0287 (Ki 270 microM). The present results show that propentofylline and its hydroxylated metabolite can influence adenosine mechanisms in a multitude of ways. How these different actions may contribute to the ability of propentofylline to reduce the magnitude of ischemic damage is discussed.
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PMID:Further evidence that propentofylline (HWA 285) influences both adenosine receptors and adenosine transport. 162 77

We examined the effects of a xanthine derivative, propentofylline, on TNFalpha production by glial cells and on infection ofglial cells with a murine leukemia virus, LP-BM5, which induces murine AIDS in susceptible mice. Propentofylline suppressed TNFalpha production in glial cells and also effectively suppressed infection ofglial cells with LP-BM5 in vitro. Addition ofTNFalpha, but not IL-1 or IL-6, abolished the suppressive effects ofpropentofylline. Anti-TNFalpha antibody also suppressed infection of LP-BM5 in these cells. These findings suggest that propentofylline suppressed LP-BM5 infection in glial cells by suppressing TNFalpha production by these cells. Because propentofylline reportedly passes through the blood-brain barrier, it may be useful in the treatment of central nervous system involvement by HIV infection or neurological diseases in which TNFalpha plays a causative role, such as multiple sclerosis.
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PMID:Propentofylline inhibits production of TNFalpha and infection of LP-BM5 murine leukemia virus in glial cells. 983 53