1. <i>Cis</i> unsaturated fatty acids were shown to inhibit porcine platelet aggregation in response to both collagen and thrombin. Fatty acids with a <i>trans</i> double bond had an anti-aggregatory effect on collagen-induced aggregation but this was significantly less than that observed with the <i>cis</i> equivalent and was diminished as the dose of agonist increased. Thrombin-induced platelet aggregation was unchanged or slightly potentiated by <i>trans</i> isomers. 2. Both the <i>cis</i> and <i>trans</i> isomeric acids inhibited collagen-induced TXB<sub>2</sub> production. The <i>trans</i> unsaturated fatty acids also inhibited TXB<sub>2</sub> production in response to thrombin, even though they did not inhibit thrombin induced platelet aggregation. 3. Unlike arachidonic acid, the <i>cis</i> and <i>trans</i> mono-unsaturated fatty acids were not rapidly incorporated into membrane phospholipids but modified platelet aggregation whilst in the free acid form. 4. Pre-incubation of platelets with either <i>cis</i> or <i>trans</i> delta 13, 18:1, selectivity inhibited the incorporation of radio-labelled arachidonic acid into membrane PS. 5. <i>Cis</i> and <i>trans</i> unsaturated delta 13, 18:1, inhibited the initial turnover of membrane PI in response to thrombin possibly by an inhibitory effect on PI-specific phospholipase C. After 5 minutes, however, the level of arachidonic acid released from both PI and PE was increased in the presence of the isomeric fatty acids. This may have been via a potentiation of the action of phospholipase A<sub>2</sub>. 6. An increased release of arachidonic acid could result in the inhibition of aggregation if metabolised via the 12-lipoxygenase pathway, as the end products of this sytem have direct anti-aggregatory activity and inhibit the cyclo-oxygenase enzymes thus reducing TXA<sub>2</sub> synthesis. 7. <i>Cis</i> unsaturated fatty acids, which produce a greater level of membrane disruption than the <i>trans</i>, may lead to more efficient channelling of the released arachidonic acid in the direction of the lipoxygenase pathway, and thereby produce a greater inhibition of aggregation. The possibility remains that the <i>cis</i> isomers have another, as yet unidentified mechanism by which they inhibit platelet aggregation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:253708 |
| Date | January 1990 |
| Creators | Peacock, Lesley |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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