997 resultados para Arakawa and Gins


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The possible molecular basis for the previously described antagonistic interactions between adenosine A1 receptors (A1R) and dopamine D1 receptors (D1R) in the brain have been studied in mouse fibroblast Ltk− cells cotransfected with human A1R and D1R cDNAs or with human A1R and dopamine D2 receptor (long-form) (D2R) cDNAs and in cortical neurons in culture. A1R and D1R, but not A1R and D2R, were found to coimmunoprecipitate in cotransfected fibroblasts. This selective A1R/D1R heteromerization disappeared after pretreatment with the D1R agonist, but not after combined pretreatment with D1R and A1R agonists. A high degree of A1R and D1R colocalization, demonstrated in double immunofluorescence experiments with confocal laser microscopy, was found in both cotransfected fibroblast cells and cortical neurons in culture. On the other hand, a low degree of A1R and D2R colocalization was observed in cotransfected fibroblasts. Pretreatment with the A1R agonist caused coclustering (coaggregation) of A1R and D1R, which was blocked by combined pretreatment with the D1R and A1R agonists in both fibroblast cells and in cortical neurons in culture. Combined pretreatment with D1R and A1R agonists, but not with either one alone, substantially reduced the D1R agonist-induced accumulation of cAMP. The A1R/D1R heteromerization may be one molecular basis for the demonstrated antagonistic modulation of A1R of D1R receptor signaling in the brain. The persistence of A1R/D1R heteromerization seems to be essential for the blockade of A1R agonist-induced A1R/D1R coclustering and for the desensitization of the D1R agonist-induced cAMP accumulation seen on combined pretreatment with D1R and A1R agonists, which indicates a potential role of A1R/D1R heteromers also in desensitization mechanisms and receptor trafficking.

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Mode of access: Internet.

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Information incorrect in publication as to sale by the Supt. of Docs.

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Includes bibliographical references.

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Issued Jan. 1977.

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"August 1943."

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Pouco mais de meio século depois da descoberta do Novo Mundo, em plena Conquista espanhola, ocorreria em Valladolid, nos anos de 1550 e 1551, um evento sem precedentes: um debate público protagonizado por duas notáveis personagens, a saber: o Frei dominicano Bartolomé de Las Casas e Juan Ginés de Sepúlveda. Este debate ficou conhecido na História como a Controvérsia de Valladolid, e teve, como principal objetivo, discutir o modo como deveriam ser tratados os índios do Novo Mundo, quais eram os seus direitos e as suas atribuições. Esta tese discute o contexto em que se deu essa controvérsia, suas personagens e, é claro, ela própria, em seus argumentos, modo de exposição e estrutura constitutiva.(AU)