Effects of tubercidin and its 5'-O-methyl ether on adenosine receptors and mediator release functions in mast cells.
Tubercidin (7-deazaadenosine, Tu) is a highly cytotoxic nucleoside xenobiotic that, as the nucleoside or nucleotide derivatives, closely mimics the actions of adenosine (or its corresponding nucleotides) in a wide variety of biochemical/biological systems. In light of its acceptance in these test systems as an adenosine (Ado) surrogate, it was postulated that the compound might interact with adenosine receptors. To test this hypothesis, a nonphosphorylatable derivative (5'-O-methyl tubercidin, MeTu) was prepared and evaluated in comparison with tubercidin and Ado in a variety of biological systems. In a cell culture assay using Chinese hamster ovary cells, MeTu is approximately one-third as cytotoxic as is Ado and 10(5)-fold less cytotoxic than Tu. Both Tu and MeTu inhibited the antigen-stimulated release of beta-hexosaminidase from mouse bone marrow derived mast cells in vitro, but only Tu was active in the in vivo PCA test. The inhibitory effect of MeTu on mast cell mediator release does not appear to involve interaction with adenosine receptors or to be the result of conversion to Tu per se.
Smith
C G
CG
Biofor, Inc., Waverly, Pennsylvania 18471, USA.
Lee
S J
SJ
Marquardt
D L
DL
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004987:Ethers; D018836:Inflammation Mediators / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D004987:Ethers; D018836:Inflammation Mediators; D018047:Receptors, Purinergic P1; D001619:beta-N-Acetylhexosaminidases; D014372:Tubercidin