In vivo release and clearance of rat platelet phospholipase A2.
Intravenous injection of ADP into rats produced a rapid increase of plasma phospholipase A2 activity with a concomitant decrease in platelet count. Phospholipase A2 activity in plasma reached a peak within 1 min and thereafter declined sharply. This phospholipase A2 activity was reactive with a monoclonal antibody specific for rat platelet-derived phospholipase A2. These findings, together with the fact that ADP is a stimulant specific for platelets, suggest that the phospholipase A2 observed may be released into plasma from activated platelets in vivo. When platelet-derived phospholipase A2 was purified, labeled with 125I, and injected intravenously into rats, the radioactivity in the plasma decreased rapidly: the half-life of the enzyme in the blood stream was less than 30 s. Addition of either heparin or anti-phospholipase A2 monoclonal antibody directed against the domain of the enzyme responsible for binding to heparin retarded the clearance of the enzyme, suggesting that phospholipase A2 might be adsorbed onto heparan sulfate proteoglycans on the endothelial cell surface. Examination of the distribution of radioactivity in vivo revealed that most of the enzyme was rapidly taken up by the liver and degraded to acid-soluble materials.
Murakami
M
M
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Kudo
I
I
Inoue
K
K
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D006493:Heparin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D009928:Organ Specificity; D010740:Phospholipases / Q000097:blood*; D010741:Phospholipases A / Q000097:blood* / Q000302:isolation & purification / Q000378:metabolism; D054467:Phospholipases A2; D015539:Platelet Activation; D010978:Platelet Factor 4 / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains
D010978:Platelet Factor 4; D000244:Adenosine Diphosphate; D006493:Heparin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2