Influence of Platelet Aggregation Modulators on Cyclic AMP Production in Human Thrombocytes

Folia Med (Plovdiv). 2018 Jun 1;60(2):241-247. doi: 10.1515/folmed-2017-0091.

Abstract

Background: Cyclic AMP is a powerful inhibitor of platelet aggregation. In the present study we examined the effect of platelet aggregation modulators on cyclic AMP content in human thrombocytes. Of the agents we tested, lactoferrin, wortmannin, quercetin and amiloride are platelet aggregation inhibitors, whereas ouabain is a platelet activator.

Aim: To investigate the effect of lactoferrin, wortmannin, quercetin, ouabain and amiloride applied alone and in combination with lactoferrin on cyclic AMP production in human platelets.

Materials and methods: 'Direct cAMP ELISA kit' was used for cyclic AMP determination.

Results: The studied modulators, individually or in combination, stimulate cyclic AMP production in platelets.

Conclusions: Wortmannin, quercetin, ouabain and amiloride increase cyclic AMP level in human platelets. Lactoferrin also increases cyclic AMP level, but the effect is statistically insignificant, which shows that lactoferrin does not participate directly in the cyclic AMP signaling. Lactoferrin additionally augments the stimulating action of wortmannin, quercetin, ouabain and amiloride on the cyclic AMP production. This probably shows a synergetic interference of lactoferrin in signal pathways along with phosphatidylinositol 3-kinase (wortmannin), quercetin (control over protein kinases, the redox state of the cell and ion transport), ouabain and amiloride (mechanisms of ion transport and phosphorylation).

Keywords: cyclic AMP; human platelets; lactoferrin.

MeSH terms

  • Amiloride / pharmacology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Cyclic AMP / metabolism*
  • Humans
  • Lactoferrin / pharmacology
  • Ouabain / pharmacology
  • Platelet Activation / drug effects*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Quercetin / pharmacology
  • Wortmannin / pharmacology

Substances

  • Platelet Aggregation Inhibitors
  • Ouabain
  • Amiloride
  • Quercetin
  • Cyclic AMP
  • Lactoferrin
  • Wortmannin