How does dipyridamole elevate extracellular adenosine concentration? Predictions from a three-compartment model of adenosine formation and inactivation.
Steady-state mathematical models are developed according to which adenosine is formed in the cytoplasm of a group of cells, arises in the extracellular space via the symmetric nucleoside transporter and is inactivated in the adenosine forming cells and after rate-limiting transport into other cell-types. Dipyridamole increases the Km and Vmax. of the transporter symmetrically with respect to influx and efflux. Models incorporating differing degrees of compartmentation are used to predict intracellular and extracellular adenosine concentration as a function of dipyridamole concentration and adenosine formation rate. The vasodilator action of dipyridamole is explained since it is predicted to elevate interstitial fluid adenosine concentrations at all rates of adenosine formation provided that washout of the interstitial compartment is restricted.
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism; D000248:Adenosine Kinase / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009705:Nucleosides / Q000037:antagonists & inhibitors
D009705:Nucleosides; D004176:Dipyridamole; D000248:Adenosine Kinase; D000243:Adenosine Deaminase; D000241:Adenosine