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Down syndrome fibroblasts are hyperresponsive to beta-adrenergic stimulation. 1981

J D McSwigan, and D R Hanson, and A Lubiniecki, and L L Heston, and J R Sheppard

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.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008297 Male Males
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011458 Prostaglandins E (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities. PGE
D011941 Receptors, Adrenergic Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction. Adrenergic Receptors,Adrenoceptor,Adrenoceptors,Norepinephrine Receptor,Receptors, Epinephrine,Receptors, Norepinephrine,Adrenergic Receptor,Epinephrine Receptors,Norepinephrine Receptors,Receptor, Adrenergic,Receptor, Norepinephrine
D011943 Receptors, Adrenergic, beta One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS. Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D002772 Cholera Toxin An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. Cholera Toxin A,Cholera Toxin B,Cholera Toxin Protomer A,Cholera Toxin Protomer B,Cholera Toxin Subunit A,Cholera Toxin Subunit B,Choleragen,Choleragenoid,Cholera Enterotoxin CT,Cholera Exotoxin,Cholera Toxin A Subunit,Cholera Toxin B Subunit,Procholeragenoid,Enterotoxin CT, Cholera,Exotoxin, Cholera,Toxin A, Cholera,Toxin B, Cholera,Toxin, Cholera
D002904 Chromosomes, Human, 21-22 and Y The short, acrocentric human chromosomes, called group G in the human chromosome classification. This group consists of chromosome pairs 21 and 22 and the Y chromosome. Chromosomes G,Group G Chromosomes,Chromosomes, Human, 21 22,Chromosomes, Human, 21-22,Chromosome, Group G,Chromosomes, Group G,Group G Chromosome
D004314 Down Syndrome A chromosome disorder associated either with an extra CHROMOSOME 21 or an effective TRISOMY for chromosome 21. Clinical manifestations include HYPOTONIA, short stature, BRACHYCEPHALY, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, single transverse palmar crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213) Mongolism,Trisomy 21,47,XX,+21,47,XY,+21,Down Syndrome, Partial Trisomy 21,Down's Syndrome,Partial Trisomy 21 Down Syndrome,Trisomy 21, Meiotic Nondisjunction,Trisomy 21, Mitotic Nondisjunction,Trisomy G,Downs Syndrome,Syndrome, Down,Syndrome, Down's
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations

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