Enhancement of A23187-induced arachidonic acid liberation by vasopressin is sensitive to genistein in rabbit platelets.
A mechanism by which vasopressin enhances phospholipase A2 activation in rabbit platelets was investigated. Stimulation of the platelets with vasopressin enhanced arachidonic acid liberation, as well as aggregation and ATP secretion in the presence of submaximal concentration of A23187, although vasopressin alone had no effect. The vasopressin-enhanced liberation was inhibited by p-bromophenacyl bromide, a phospholipase A2 inhibitor, and by genistein, a tyrosine kinase inhibitor. Though epinephrine also caused a similar enhancement of the liberation, this effect of epinephrine was insensitive to genistein. Staurosporine, a protein kinase C inhibitor, completely suppressed phorbol 12-myristate 13-acetate-enhanced arachidonic acid liberation, but suppressed the vasopressin-induced enhancement only slightly. These results suggest that vasopressin-enhanced phospholipase A2 activation may be regulated by a genistein-sensitive mechanism, most likely by a protein tyrosine kinase-mediated pathway, but not by guanine nucleotide-binding protein- or protein kinase C-mediated pathway.
Akiba
S
S
Department of Biochemistry, Kyoto Pharmaceutical University, Japan.
Sato
T
T
Fujii
T
T
D000098:Acetophenones / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology*; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology*; D010741:Phospholipases A / Q000097:blood; D054467:Phospholipases A2; D010974:Platelet Aggregation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*
D000098:Acetophenones; D000470:Alkaloids; D007529:Isoflavones; D014667:Vasopressins; D016718:Arachidonic Acid; D000001:Calcimycin; D000255:Adenosine Triphosphate; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; C006821:4-bromophenacyl bromide; D004837:Epinephrine