Abnormalities of 5-hydroxytryptamine uptake and binding by blood platelets from children with Down's syndrome.

1. Blood platelets from normal children and children with the trisomy 21 form of Down's syndrome (mongolism) were studied to determine the cause of the well established reduction in platelet 5-HT in the disease.2. Concentrations of endogenous 5-HT in the platelets from mongols were 25.3% of the concentrations found in normal children.3. The net accumulation of 5-HT in the mongol cells was decreased to 52.7% of normal. This reduction was probably due, in part, to a defect in 5-HT transport, because the initial rates of 5-HT uptake at plasma concentrations of 10(-6) and 10(-5)M were significantly slower.4. Experiments on the efflux of 5-HT from mongol platelets loaded with amine showed that the rate of loss was initially 2.6 and later 7.8 times faster than normal.5. Platelet ATP in mongol cells was 26% of normal, and the reduction of ATP and 5-HT was in the molar ratio of 3:1.6. It is considered that the low platelet 5-HT in Down's syndrome is due to a defective 5-HT transport mechanism and impaired 5-HT binding, resulting from a reduction in the essential binding substance, ATP.