ABSTRACT
Forty-one high-functioning individuals with autism between the ages of 7 and 36 and an age and intelligence matched comparison group were investigated in their ability to recognized emotions in photographs. A colour identification task served as control condition. The autistic group was significantly impaired on the emotions task only. There was no substantial difference between groups in the structures underlying their emotional concepts (pleasantness and arousal). However, there is a trend for the autistic group to rely on other strategies in the recognition of emotions than the comparison group. These strategies may be insufficient in the appreciation of facial expressions.
Subject(s)
Autistic Disorder/psychology , Concept Formation , Emotions , Adolescent , Adult , Arousal , Autistic Disorder/diagnosis , Child , Facial Expression , Female , Humans , Intelligence , Male , Mental Recall , Problem SolvingABSTRACT
3T3-F442A adipocytes, which express major beta 3-adrenergic receptors (beta 3-AR) (90%) and minor beta 1-AR (< 10%) and beta 2-AR (< 1%) populations, were used to investigate regulation by n-butyric acid of beta-AR subtype expression. Following butyrate treatment, EC50 values of beta 1- and beta 2-selective agonists, dobutamine and fenoterol, were decreased, whereas that of the beta 3-selective agonist BRL37344 was increased. Direct binding and competition of (-)-[125I]iodocyanopindolol binding by selective beta 1- and beta 2-AR antagonists, CGP20712A and ICI118551, and by the beta 3-AR agonist, BRL37344, revealed that both beta 1- and beta 2-AR were increased in butyrate-treated adipocytes, whereas beta 3-AR almost totally disappeared. In control adipocytes, beta 1-, beta 2-, and beta 3-AR transcripts (quantitated by a polymerase chain reaction assay) represented 6.5, 0.5, and 93% of total beta-AR mRNA, respectively. In butyrate-exposed cells, proportions of beta-AR proteins and mRNAs were, respectively, 87 and 94% for beta 1 and 9 and 1% for beta 2-AR. beta 3-ARs were barely detectable in binding assays and accounted for 4.5% of beta-AR transcripts. Variations of beta-AR protein and mRNA levels were accompanied by parallel changes in the transcription rates of the corresponding genes. The differential regulation of the three beta-ARs by n-butyric acid, a dietary factor produced from colonic fermentation, may have significant nutritional and energetic consequences.
Subject(s)
Adipocytes/metabolism , Butyrates/pharmacology , Gene Expression Regulation/drug effects , Receptors, Adrenergic, beta-1/biosynthesis , Receptors, Adrenergic, beta-2/biosynthesis , Receptors, Adrenergic, beta/biosynthesis , 3T3 Cells , Adenylyl Cyclase Inhibitors , Adipocytes/drug effects , Adrenergic beta-1 Receptor Antagonists , Adrenergic beta-2 Receptor Antagonists , Animals , Base Sequence , Butyric Acid , DNA Primers , DNA, Complementary/biosynthesis , Ethanolamines/pharmacology , Imidazoles/pharmacology , Iodocyanopindolol , Isoproterenol/pharmacology , Mice , Molecular Sequence Data , Oligonucleotides, Antisense , Pindolol/analogs & derivatives , Pindolol/metabolism , Polymerase Chain Reaction , Propanolamines/pharmacology , Receptors, Adrenergic, beta/drug effects , Receptors, Adrenergic, beta/metabolism , Receptors, Adrenergic, beta-1/metabolism , Receptors, Adrenergic, beta-2/metabolism , Receptors, Adrenergic, beta-3 , Transcription, Genetic/drug effectsABSTRACT
Expression of mRNA for beta 1-, beta 2-, and beta 3-adrenergic receptors (beta 1-, beta 2-, and beta 3-AR) was investigated in human tissues. beta 1- and beta 2-AR mRNA distribution correlated with that of the cognate receptors established by pharmacological studies. beta 3-AR transcripts were abundant in infant perirenal brown adipose tissue, characterized by the presence of uncoupling protein (UCP) mRNA. In adult whole adipose tissues, beta 3-AR mRNA levels were high in deep deposits such as perirenal and omental, and lower in subcutaneous. In these deposits, UCP mRNA levels paralleled those of beta 3-AR. However, isolated omental and subcutaneous adipose cells, enriched in white adipocytes, expressed beta 3-AR but no UCP transcripts. beta 3-AR mRNA was highly expressed in gallbladder, and to a much lower extent in colon, independently of UCP mRNA. Quadriceps or abdominal muscles, heart, liver, lung, kidney, thyroid, and lymphocytes did not express intrinsic beta 3-AR mRNA. This study demonstrates that substantial amounts of brown adipocytes exist throughout life in adipose deposits, which are generally classified as white. These deposits are the main sites of beta 3-AR expression, which also occurs in gallbladder and colon. beta 3-AR may thus be involved in the control of lipid metabolism, possibly from fat assimilation in the digestive tract, to triglyceride storage and mobilization in adipose tissues.
Subject(s)
RNA, Messenger/analysis , Receptors, Adrenergic, beta/genetics , Adipose Tissue/physiology , Adult , Aged , Base Sequence , Blotting, Northern , Child , Child, Preschool , Female , Heart/physiology , Humans , Infant , Infant, Newborn , Male , Middle Aged , Molecular Sequence Data , Oligonucleotides, Antisense , Organ Specificity , Polymerase Chain Reaction , RNA, Messenger/genetics , Receptors, Adrenergic, beta/classificationABSTRACT
Modulation of beta 3-adrenergic receptor (beta 3AR) expression by dexamethasone was investigated in the murine 3T3-F442A adipocytic cell line. In untreated cells, a major population of binding sites (62,000-114,000 sites/cell) of low affinity for (-)-[3H] CGP12177 and (-)-[125I]iodocyanopindolol (corresponding to the beta 3AR subtype) was present along with a minor population (6,500-8,000 sites/cell) of sites of high affinity for the radioligands (corresponding to a mixture of the beta 1 and beta 2AR subtypes). Long-term exposure of the cells to 250 nM dexamethasone led to a sharp decrease in beta 3AR density (less than 5,000 sites/cell) which paralleled a diminished potency of the beta 3AR-selective agonists BRL37344 and CGP12177 to stimulate the production of intracellular cAMP. Analysis of RNA by polymerase chain reaction and nuclear run-on assays indicated that dexamethasone inhibited the synthesis of beta 3AR mRNA, resulting in 4-8-fold decrease in the steady-state levels of this mRNA. The down-regulation of beta 3AR protein and cellular mRNA appeared to be mediated by the receptor for glucocorticoids as assessed by the antagonistic action of the anti-glucocorticoid RU38486.
Subject(s)
Adipose Tissue/physiology , Adrenergic beta-Agonists/pharmacology , Dexamethasone/pharmacology , Ethanolamines/pharmacology , Isoproterenol/pharmacology , Receptors, Adrenergic, beta/physiology , Transcription, Genetic , 3T3 Cells , Adenylyl Cyclases/metabolism , Adipose Tissue/drug effects , Animals , Base Sequence , Cell Membrane/metabolism , Dose-Response Relationship, Drug , Kinetics , Mice , Mifepristone/pharmacology , Molecular Sequence Data , Oligodeoxyribonucleotides , Oligonucleotides, Antisense , Polymerase Chain Reaction , Progesterone/pharmacology , Propanolamines/pharmacology , RNA/genetics , RNA/isolation & purification , Receptors, Adrenergic, beta/drug effects , Receptors, Adrenergic, beta/genetics , Transcription, Genetic/drug effectsABSTRACT
Expression of ligand binding properties for an atypical beta-adrenergic receptor (beta-AR) subtype was studied during the adipose differentiation of murine 3T3-F442A cells and compared with that of the human beta 3-AR expressed in Chinese hamster ovary cells stably transfected with the human beta 3-AR gene (CHO-beta 3 cells) Emorine, L. J., Marullo, S., Briend-Sutren, M. M., Patey, G., Tate, K., Delavier-Klutchko, C., and Strosberg, A. D. (1989) Science 245, 1118-1121). 3T3-F442A adipocytes exhibited high and low affinity binding sites for (-)-4-(3-t-butylamino-2-hydroxypropoxy) [5,7-3H]benzimidazole-2-one ((-)-[3H]CGP-12177) (KD = 1.2 and 38.3 nM) and (-)-[125I]iodocyanopindolol ([125I]CYP) (KD = 47 and 1,510 pM). The high affinity sites corresponded to the classical beta 1- and beta 2-AR subtypes whereas the KD values of the low affinity sites for the radioligands were similar to those measured in CHO-beta 3 cells (KD = 28 nM and 1,890 pM for (-)-[3H]CGP12177 and [125I]CYP, respectively). These low affinity sites were undetectable in preadipocytes but represented about 90% of total beta-ARs in adipocytes. The atypical beta-AR and the human beta 3-AR add similarly low affinities (Ki = 3-5 microM) for (+/-)-(2-(3-carbamoyl-4-hydroxyphenoxy)ethylamino-3)-(4-(1-methyl- 4- trifluormethyl-2-imidazolyl)-phenoxy)-2-propanol methane sulfonate (CGP20712A) or erythro-(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylaminob utan-2-ol (ICI118551), highly selective beta 1- and beta 2-AR antagonists, respectively, in agreement with the poor inhibitory effect of the compounds on (-)-isoproterenol (IPR)-stimulated adenylate cyclase activity. Atypical beta-AR and beta 3-AR had an affinity about 10-50 times higher for sodium-4-(2-[2-hydroxy-2-(3-chlorophenyl)ethylamino]propyl)phenoxyace tate sesquihydrate (BRL37344) than the beta 1-AR subtype. This correlates with the potent lipolytic effect of BRL37344 in adipocytes. The rank order of potency of agonists in functional and binding studies was BRL37344 greater than IPR less than (-)-norepinephrine greater than (-)-epinephrine both in 3T3 adipocytes and CHO-beta 3 cells. As in CHO-beta 3 cells, the classical beta 1- and beta 2-antagonists CGP12177, oxprenolol, and pindolol were partial agonists in adipocytes. Although undetectable in preadipocytes, a major mRNA species of 2.3 kilobases (kb) and a minor one of 2.8 kb were observed in adipocytes by hybridization to a human beta 3-AR specific probe.(ABSTRACT TRUNCATED AT 400 WORDS)
Subject(s)
Adipose Tissue/metabolism , Receptors, Adrenergic, beta/metabolism , 3T3 Cells , Adipose Tissue/cytology , Adrenergic beta-Antagonists , Animals , Base Sequence , Binding, Competitive , Blotting, Northern , DNA/genetics , Ethanolamines/pharmacology , Humans , Imidazoles/pharmacology , Mice , Molecular Sequence Data , Oxprenolol/pharmacology , Pindolol/pharmacology , Polymerase Chain Reaction , Propanolamines/pharmacology , RNA, Messenger/genetics , Receptors, Adrenergic, beta/drug effects , Receptors, Adrenergic, beta/geneticsABSTRACT
Hybridization of a poorly immunogenic tumor cell with an allogeneic cell was performed in order to improve tumor immune response; several variants derived from one hybrid tumor cell were studied. We compared the immunogenicity of these variants and their allogeneic and syngeneic class I antigen expression before and after IFN gamma treatment. Allogeneic class I antigens were weakly expressed in all variants; IFN treatment enhanced their expression similarly in both immunogenic and nonimmunogenic variants. Syngeneic class I antigen expression differed among variants: IFN treatment induced changes in their expression which corresponded to a posttranscriptional event and which could, at least partly, explain the modifications observed in their immunogenicity.