Effect of berbamine on cytosolic phospholipase A2 activation in rabbit platelets.
The effect of berbamine, a biscoclaurine alkaloid, on cytosolic phospholipase A2 activation in rabbit platelets was investigated. Berbamine inhibited arachidonic acid liberation induced by thrombin but not that by ionomycin. The alkaloid did not affect thrombin-stimulated Ca2+ mobilization. Ca(2+)-dependent translocation of cytosolic phospholipase A2 to membranes, or the activity of partially purified cytosolic phospholipase A2. Furthermore, berbamine had no effect on the thrombin-elicited increase in cytosolic phospholipase A2 activity. However, berbamine suppressed arachidonic acid liberation in platelets stimulated with GTP-binding protein activators. Although incubation of platelet membranes with a GTP analogue decreased the islet-activating protein-catalyzed ADP-ribosylation of an approximately 40 kDa protein in the membranes, pretreatment of the membranes with berbamine did not influence the decrease in ADP-ribosylation. These results suggest that berbamine may impair GTP-binding protein-mediated activation of cytosolic phospholipase A2, probably without influencing the enzyme translocation to membranes or the increase in the enzyme activity, and thus may cause the suppression of thrombin-induced arachidonic acid liberation.
Akiba
S
S
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Japan.
Nagatomo
R
R
Ishimoto
T
T
Sato
T
T
D000470:Alkaloids / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000032:analysis; D044182:Benzylisoquinolines; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011817:Rabbits; D012969:Sodium Fluoride / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors
D000470:Alkaloids; D017607:Aluminum Compounds; D000894:Anti-Inflammatory Agents, Non-Steroidal; D044182:Benzylisoquinolines; D002712:Chlorides; D016718:Arachidonic Acid; D000077410:Aluminum Chloride; D015759:Ionomycin; D012969:Sodium Fluoride; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin; D002118:Calcium; C027870:berbamine