Suppressive effect of biscoclaurine alkaloids on agonist-induced activation of phospholipase A2 in rabbit platelets.
The effect of biscoclaurine (bisbenzylisoquinoline) alkaloids on phospholipase A2 and C activation in signal transduction system of rabbit platelet was studied. Isotetrandrine, cepharanthine and berbamine inhibited the aggregation induced by collagen but not by other stimuli such as thrombin and arachidonic acid, while tetrandrine equally inhibited the aggregation by any of these agonists. All these four alkaloids suppressed arachidonic acid liberation in response to collagen or thrombin, but not diacylglycerol formation and increase in cytoplasmic Ca2+ concentration in response to thrombin or arachidonic acid. In saponin-permeabilized platelets, they also suppressed arachidonic acid liberation induced by an addition of both GTP gamma S and Ca2+, whereas the liberation induced by an addition of Ca2+ alone was not prevented by them. These data suggest that isotetrandrine, cepharanthine and berbamine have a rather specific potency to suppress the phospholipase A2 activation by a mechanism other than direct inhibition of the enzyme or interference with the ligand-receptor interaction. They seem, at least in part, to exert the effect on the GTP-binding protein-phospholipase A2 complex in the platelet signal transduction system. In contrast, tetrandrine appears to inhibit a step following an increase in cytosolic free Ca2+ concentration in the agonist-induced signal transduction system, in addition to suppressing the phospholipase A2 activation.
Hashizume
T
T
Department of Biochemistry, Kyoto Pharmaceutical University, Japan.
Yamaguchi
H
H
Sato
T
T
Fujii
T
T
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002118:Calcium / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D002118:Calcium; D003094:Collagen; D019204:GTP-Binding Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010741:Phospholipases A; D054467:Phospholipases A2; D010975:Platelet Aggregation Inhibitors; C009438:tetrandrine; C006947:cepharanthine; D052117:Benzodioxoles; C027870:berbamine