Abstract
Summary: The mechanism of low serotonin content in Down's syndrome (DS) platelets was studied by comparing the activity of (Na+/K+)-ATPase, ouabain binding, and rate of outward movement of sodium in platelets from DS and control subjects.
Ouabain inhibited (Na+/K+)-ATPase activity in sodium iodide-extracted platelet membranes from 10 normal subjects had an average value of 2.87 ± 0.20 μmol Pi./hr/109 platelets whereas the activity from DS platelet membranes was 2.13 ± 0.19 μmol Pi/hr/109 platelets (P < 0.02). Total ATPase activity in normal platelet membranes was 3.58 ± 0.33 μmol Pi/hr/109 platelets whereas that from DS membranes was 2.49 ± 0.35 μmol Pi/hr/109 platelets (P < 0.02). (Na+/K+)-ATPase activity is decreased in DS platelets.
Ouabain binds specifically to (Na+/K+)-ATPase sites on membranes. The amount of ouabain bound by DS platelets is less than that by control platelets. The average amount of ouabain bound was 1.08 ± 0.04 × 10-15 mol/109 platelets for controls and 0.86 ± 0.02 × 10-15 mol/109 platelets for DS (P < 0.001). There appear to be fewer (Na+/K+)-ATPase sites on DS platelets compared to normal.
The outward movement of Na+ in platelets is catalyzed by the enzyme (Na+K+)-ATPase. The average ouabain-sensitive outward movement of sodium in normal platelets was 9.03 ± 0.46 μmol/hr/109 platelets. For DS subjects the average outward movement was 50% of normal, 4.41 ± 0.14 /μmol/hr/109 platelets. The rate of outward Na+ transport is significantly less (P < 0.001) in DS compared to normal platelets.
Decreased serotonin content of DS platelets may be secondary to decreased (Na+/K+)-ATPase activity, which results in decreased rate of outward Na+ transport and increased Na+ content. As serotonin is cotransported with Na+, the decreased rate of serotonin uptake may be secondary to increased Na+ content of DS platelets.
Speculation: If decreased (Na+/K+)-ATPase activity, decreased rate of Na+ outward transport, increased Na+ content, and decreased rate of serotonin uptake were also present in synaptosomes of DS patients, decrease in amine content might occur and result in altered ncurotransmission.
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Mccoy, E., Enns, L. Sodium Transport, Ouabain Binding, and (Na+/K+)-ATPase Activity in Down's Syndrome Platelets. Pediatr Res 12, 685–689 (1978). https://doi.org/10.1203/00006450-197806000-00001
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DOI: https://doi.org/10.1203/00006450-197806000-00001
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