5'-Deoxy-5'-methylthioadenosine inhibition of rat T lymphocyte phosphodiesterase: correlation with inhibition of Con A induced proliferation.
5'-Deoxy-5'-methylthioadenosine inhibits Concanavalin A induced rat T lymphocyte proliferation in a dose dependent manner (50 microM to 1000 microM). The extent of inhibition by MTA of lymphocyte proliferation was greatest when MTA was added to the cells at the same time as Concanavalin A. The determination of cyclic AMP level from 30 min to the 6th hour shows that 5'-Deoxy-5'-methylthioadenosine inhibition is correlated with an elevation of cyclic AMP at this mitogen recognition phase. 5'-Deoxy-5'-methylthioadenosine concentrations that inhibit rat T lymphocyte proliferation also inhibit phosphodiesterase activity. This biochemical mechanism could be specific to 5'-Deoxy-5'-methylthioadenosine inhibition since in an another model of inhibition of rat T lymphocyte proliferation (2'-Deoxyadenosine 10 microM, in adenosine deaminase deficiency conditions: 2'-Deoxycoformycin 10 microM), no significant modification of cyclic AMP level can be demonstrated.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D003839:Deoxyadenosines; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D013872:Thionucleosides / Q000494:pharmacology*
D003839:Deoxyadenosines; D010726:Phosphodiesterase Inhibitors; D013872:Thionucleosides; D003208:Concanavalin A; C008500:5'-methylthioadenosine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000241:Adenosine