Effects of ouabain on 86Rb-uptake, 3H-5-HT-uptake and aggregation by 5-HT and ADP in human platelets.
In the search of sensitive models for actions of digitalis-like substances on intact cells or tissues, the effects of ouabain on human platelets were investigated. In a concentration-dependent manner ouabain 10(-8)-10(-4) M inhibited Na+-K+-ATPase activity measured as uptake of 86Rubidium (86Rb), with about 90% inhibition of the total uptake at ouabain greater than or equal to 10(-6) M. An almost identical concentration-effect curve was found for platelet uptake of 3H-serotonin (3H-5-HT). The platelet shape change reaction to exogenous 5-HT (1 X 10(-6) M) was suppressed by ouabain (10(-8)-10(-4) M) in a concentration-dependent manner, but with no clear maximum effect within the range tested. Aggregation induced by adenosine-di-phosphate (ADP 2 X 10(-6) M) was enhanced by ouabain 10(-8)-10(-6) M. At the highest concentration tested the rate of aggregation was increased by 31% and the change in light transmission by 54%. At low concentrations (less than 10(-9) M) of ouabain, there was a tendency towards increased aggregation as well as increased uptake of 86Rb, which may be a parallel to observations of positive inotropic effects of low concentration of glycosides, which do not inhibit Na+-K+-ATPase. The results show that human platelets can be used as a model tissue for studying effects of cardiac glycosides. This suggests that it may be useful for further investigations of the biological effects of agents with a similar effect profile, e.g. endogenous digitalis-like substances.
Andersson
T L
TL
Department of Clinical Pharmacology, University Hospital, Lund, Sweden.
Vinge
E
E
D000244:Adenosine Diphosphate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010042:Ouabain / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D012413:Rubidium / Q000378:metabolism*; D012414:Rubidium Radioisotopes; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology
D012414:Rubidium Radioisotopes; D012701:Serotonin; D010042:Ouabain; D000244:Adenosine Diphosphate; D012413:Rubidium