title: 1-O-hexadecyl-2-metoxy-glycero-3-phosphatidylcholine--a methoxy ether lipid inhibiting platelet activating factor-induced platelet aggregation and neutrophil oxidative metabolism.
abstract: Whether or not two alkylglycerols could initiate a functional response in human platelets or modify responses induced by platelet activating factor (PAF) was evaluated. It was found that 1-100 microM 1-O-hexadecyl-2-metoxy-glycero-3-phosphatidylcholine (Et-16-OCH3) induced platelet aggregation but 1-O-hexadecyl-sn-glycerol (chimyl alcohol; CA) did not. Et-16-OCH3-induced platelet aggregation was abolished by pretreatment with the PAF receptor antagonist WEB 2086. While CA had no effect on platelet aggregation induced by PAF, pretreatment with Et-16-OCH3 (0.1 microM or higher) significantly inhibited platelet aggregation induced by PAF, but had no effect on aggregation caused by ADP, thrombin or phorbol myristate acetate (PMA). A receptor binding study using radiolabelled [3H]WEB 2086 showed that Et-16-OCH3 exerts its actions through interaction with the PAF receptor. Moreover, Et-16-OCH3 inhibited neutrophil chemiluminescence responses induced by PAF, but not reactions to PMA or a formyl peptide. Finally, 1 microM Et-16-OCH3 induced a rise in the intracellular calcium concentration in platelets equal to that induced by PAF and also had an calcium ionophore-like effect at 100 microM. Thus, this study shows that Et-16-OCH3 is both a potent inducer of platelet aggregation and an inhibitor of PAF-induced platelet aggregation and neutrophil chemiluminescence, through interaction with the PAF receptor.
authors.affiliation: Department of Clinical Chemistry, Stockholm Söder Hospital, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Le Blanc
authors.forename: J
authors.initials: J
authors.lastname: Samuelsson
authors.forename: J
authors.initials: J
authors.lastname: Brohult
authors.forename: A
authors.initials: A
authors.lastname: Berg
authors.forename: J
authors.initials: J
authors.lastname: Palmblad
mesh_terms: D001381:Azepines / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; C050186:1-hexadecyl-2-methoxyglycero-3-phosphocholine; D002118:Calcium