title: Down syndrome fibroblasts are hyperresponsive to beta-adrenergic stimulation.
abstract: The hormonal response to human skin fibroblasts after exposure to beta-adrenergic agonists, prostaglandin E1 (PGE1), and cholera toxin was monitored by intracellular cyclic AMP accumulation. Down syndrome (DS; trisomy 21) cells had an approximately 10-fold greater response to beta-adrenergic agonists than did either normal diploid skin fibroblasts or other aneusomic fibroblast strains (trisomy 13, 18, and 22). The altered response in DS fibroblasts was specific for beta-adrenergic agonists, because treatment of DS or control cells with PGE1 or cholera toxin resulted in the same degree of cyclic AMP accumulation. Experiments with 3-isobutyl-1-methylxanthine, a cyclic nucleotide phosphodiesterase inhibitor, indicated that the increased response of DS fibroblasts was not primarily a function of altered cyclic AMP degradation. Monosomy 21 cells responded less than normal diploid fibroblasts to stimulation by the beta-adrenergic agonist isoproterenol. These findings suggest that genetic information on chromosome 21 participates in regulating the beta-adrenergic response of human fibroblasts.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D002904:Chromosomes, Human, 21-22 and Y; D000242:Cyclic AMP / Q000096:biosynthesis; D004314:Down Syndrome / Q000503:physiopathology*; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
chemical_list: D011458:Prostaglandins E; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine