Serotonin secretion from human platelets may be modified by Ca2+-activated, phospholipid-dependent myosin phosphorylation.
1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H-7), which has been identified as a potent inhibitor of protein kinase C in vitro (Hidaka, H., Inagaki, M., Kawamoto, S., and Sasaki, Y. (1984) Biochemistry, in press), enhanced serotonin release from human platelets that was induced by the 12-O-tetradecanoyl phorbol 13-acetate and correspondingly decreased incorporation of radioactive phosphate into a 20,000-dalton protein. H-7 did not affect the protein phosphorylation or the serotonin secretion in unstimulated platelets. A phosphopeptide with a molecular weight of 20,000 has previously been identified as a light chain (LC20) of platelet myosin and both protein kinase C and Ca2+-calmodulin-dependent myosin light-chain kinase have been shown to be involved in its phosphorylation. Two-dimensional peptide mapping following tryptic hydrolysis revealed that H-7 selectively inhibited the protein kinase C-catalyzed phosphorylation of myosin light chain. This pharmacological evidence suggests that Ca2+-activated, phospholipid-dependent myosin light-chain phosphorylation may play an inhibitory role in the release reaction.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D008970:Molecular Weight; D009218:Myosins / Q000097:blood*; D010446:Peptide Fragments / Q000032:analysis; D010743:Phospholipids / Q000097:blood*; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000097:blood*; D012701:Serotonin / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007546:Isoquinolines; D010446:Peptide Fragments; D010743:Phospholipids; D010879:Piperazines; D012701:Serotonin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011494:Protein Kinases; D011493:Protein Kinase C; D009218:Myosins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium