Is defibrotide's activity on leukocytes adenosine-receptor mediated? An "in vitro"--"ex vivo" appraisal.
Defibrotide both "in vitro" and "ex vivo" decreases PMN adhesion to nylon columns. This activity is blunted by 8-phenyltheophylline, a known blocker of adenosine A1/A2 receptors, suggesting that Defibrotide acts on that kind of receptors. Indomethacin, a blocker of PGI2 synthesis, did not cancel DFT's activity, suggesting that PGI2 is not involved in DFT's activity, at least under our experimental conditions. Non-PMN leukocytes behaved differently "ex vivo" than PMNs. DFT's activity was not blunted by 8-phenyltheophylline, suggesting that DFT acts on this kind of cell through a different mechanism. The "in vitro" experiment did not confirm "ex vivo" studies suggesting that in the "in vitro" experiment "something" is missing that is present in "ex vivo" experiments.
Alberico
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P
CRINOS Biological Research Laboratories, Villa Guardia (CO), Italy.
Porta
R
R
Pescador
R
R
Ferro
L
L
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; D018047:Receptors, Purinergic P1; C036901:defibrotide; D013806:Theophylline; C028322:8-phenyltheophylline