Acetal phosphatidic acids: novel platelet aggregating agents

Publisher Website
Google Scholar
Abstract
Palmitaldehyde, olealdehyde and linolealdehyde acetal phosphatidic acids induced rapid shape change and dose-dependent biphasic aggregation of human platelets in platelet-rich plasma; aggregation was reversible at low doses and irreversible at high doses of the acetal phosphatidic acids. The palmitaldehyde congener elicited monophasic dose-dependent aggregation of sheep platelets in platelet-rich plasma. The threshold concentration for palmitaldehyde acetal phosphatidic acid (PGAP)-induced platelet aggregation was 2.5-5 .mu.M for human platelets and 0.25-0.5 .mu.M for sheep platelets. PGAP was 4-5 times as potent vs. human platelets as the olealdehyde and linolealdehyde acetal phosphatidic acids, which were equipotent. PGAP-induced irreversible aggregation of [14C]-5-hydroxytryptamine ([14C]-5-HT)-labeled human platelets in platelet-rich plasma was accompanied by release of 44.0 .+-. 2.4% (SE) of the platelet [14C]-5-HT; reversible aggregation was not associated with release. PGAP-induced release of [14C]-5-HT-labeled sheep platelets was dose-dependent. The ADP antagonist, 2-methylthio-AMP, and the cyclo-oxygenase inhibitor, aspirin, abolished PGAP-induced 2nd phase aggregation and release in human platelets but did not affect the 1st, reversible, phase of aggregation. Both the 1st and 2nd phases of PGAP-induced aggregation were abolished by chlorpromazine, by the phospholipase A2 inhibitor, mepacrine and by nmol concentrations of prostaglandin E1 (PGE1); these agents abolished the 2nd, but not the 1st phase of ADP-induced aggregation. The related phospholipids, lecithin, lysolecithin and phosphatidic acid, at < 100 .mu.M, neither induced aggregation of human platelets in platelet-rich plasma, nor modified PGAP-induced aggregation; 1-palmityl lysophosphatidic acid elicited aggregation of human platelets at a threshold concentration of 100 .mu.M. The acetal phosphatidic acids evidently induce platelet aggregation per se by direct action at the platelet membrane, and the acetal function is of primary importance in their potent platelet-stimulating activity. As the acetal phosphatidic acids are the major components of the smooth muscle-contracting acidic phospholipid tissue extract Darmstoff, their potent platelet-aggregating properties may be of physiological or pathological significance.

This publication has 29 references indexed in Scilit: