RESUMO
The aim of the work is to study the mechanisms of the interaction of risperidone with human and bovine serum albumins using the fluorescence quenching technique. Risperidone is an atypical antipsychotic drug used to treat many psychiatric disorders. We selectively excited the fluorescence of tryptophan residues with a 290 nm wavelength light, and observed quenching by titrating human and bovine serum albumin solutions with risperidone. Emission spectra were recorded in the range from 300 to 450 nm for each quencher addition. Stern-Volmer graphs were plotted and quenching constants were estimated. Results showed that the drug quenches the fluorescence of the human serum albumin by the formation of a complex risperidone-albumin. Association constants calculated from Stern-Volmer equation for low concentrations (lower than 1:10 ratio risperidone/albumin) were of 2.56 × 10(5)M(-1), at 25 °C, and 1.43 × 10(5)M(-1), at 37 °C. As the quenching intensity of bovine serum albumin, which contains two tryptophan residues, was found to be higher than that of human serum albumin, which contains only one tryptophan residue. Hence, we suggest that the primary binding site for risperidone in albumin should be located in sub domain IB.
Assuntos
Antipsicóticos/metabolismo , Risperidona/metabolismo , Albumina Sérica/metabolismo , Animais , Antipsicóticos/química , Sítios de Ligação , Bovinos , Humanos , Ligação Proteica , Estrutura Terciária de Proteína , Risperidona/química , Albumina Sérica/química , Soroalbumina Bovina/metabolismo , Espectrometria de Fluorescência , TriptofanoRESUMO
A new application for the nuclear imaging techniques is the study of organic responses to stress. Neuroimaging techniques allow the assessment of brain activation changes in association with the metabolic responses to stress. In this paper, a review of general effects of the stress on organic activity is made, emphasizing important advances introduced by studies using PET and fMRI. The importance of the hypothalamus-pituitary-adrenal axis to onset the adequate psychical and organic responses to sustain the homeostasis during the stress is discussed, as well as the possibility of traumatic stressing experiences have negative effects on the brain.
Uma nova aplicação para as técnicas de imagem nuclear é o estudo de respostas orgânicas ao estresse. Técnicas de neuroimagem permitem observar as mudanças da ativação cerebral associadas às respostas metabólicas ao estresse. Neste artigo, uma revisão dos efeitos do estresse sobre a atividade orgânica é feita, enfatizando importantes avanços introduzidos por estudos realizados com PET e fMRI. A importância do eixo hipotálamo-hipófise-adrenal para o disparo das respostas orgânicas e psíquicas para a manutenção da homeostasia durante o estresse é discutida, bem como a possibilidade de experiências estressantes traumáticas exercerem efeitos negativos sobre o cérebro.