The adrenergic responsiveness of Down syndrome cells

Platelets and cultured fibroblasts were used to examine the hormonal response of normal diploid and Down syndrome (trisomy 21) cells. An enhanced physiological response to catecholamine hormones was found in the trisomy 21 cells. This effect was specific for the adrenergic agonists since other hormones showed equivalent responses in the normal diploid and trisomy 21 cell types. Radioligand analysis of the alpha-adrenergic receptors in trisomy 21 platelets indicated no significant difference in receptor density or ligand affinity. Enzymatic analysis of the platelet adenylate cyclase activity in vitro showed no major changes in catecholamine sensitivity between the normal and Down syndrome preparations. Somatic cell genetic studies using human-hamster hybrids indicated that a gene coding for the beta-adrenergic receptor was not located on chromosome 21 but on human chromosome 5. These receptor, enzymic, and somatic cell genetic studies argue against a gene-dosage effect involving either the adrenergic hormone receptors or a component of the adenylate cyclase enzyme in the trisomy 21 cells. Identifying the gene(s) on chromosome 21 and the molecular mechanism(s) responsible for the exaggerated response of Down syndrome cells to catecholamines are the current objectives of this research program.