In vitro effect of D-myo-inositol 1,2,6-trisphosphate (PP-56) on aggregation of platelets from normal and diabetic rats: relationship to malondialdehyde release and phosphoinositide pathway.
In the present study, we investigated the in vitro effects of D-myo-inositol 1,2,6-trisphosphate (PP-56) on platelets from normal and streptozotocin-induced diabetic rats. PP-56 markedly inhibited aggregation, in a dose-related manner, when added in vitro, more efficiently with thrombin- than with ADP-induced aggregation and, after 90 min incubation, more in diabetic than in normal platelets. The PP-56 platelet inhibitory effect seems to be related to its phosphate content. PP-56 blocked the release of malondialdehyde from erythrocytes, but to the same extent in normal and diabetic rats. PP-56, after 20 min incubation, restored the platelet phosphoinositide turnover, which was significantly modified in diabetic rats. This last observation could explain at least part of the specificity of PP-56 for normalizing platelet aggregation in diabetic animals after long-term administration in vivo.
Institut national de la santé et de la recherche médicale, Unit 63, Bron, France.
J C
JC
Ruf
M
M
Ciavatti
T
T
Gustafsson
S
S
Renaud
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007294:Inositol / Q000097:blood; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood*; D010716:Phosphatidylinositols / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002614:Chelating Agents; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010975:Platelet Aggregation Inhibitors; D007294:Inositol; D008315:Malondialdehyde; C059368:atrinositol