RESUMO
The tridecapeptide neurotensin (NT) acts in the mammalian brain as a primary neurotransmitter or neuromodulator of classical neurotransmitters. Morphological and functional in vitro and in vivo studies have demonstrated the existence of close interactions between NT and dopamine both in limbic and in striatal brain regions. Additionally, biochemical and neurochemical evidence indicates that in these brain regions NT also plays a crucial role in the regulation of the aminoacidergic signalling. Immune cells, such as lymphocytes, macrophages and mast cells are reported to be activated by neuropeptides, such as neurotensin; this activation leads to cytokine and immunoglobulin production. In addition, neurotensin increases calcium level and the production of nitric oxide. Therefore neurotensin is deeply involved in immunity and inflammation but its real function still remains to be elucidated.
Assuntos
Neurotensina/fisiologia , Neurotransmissores/fisiologia , Animais , Comportamento/fisiologia , Química Encefálica , Trato Gastrointestinal/fisiologia , Humanos , Neurotensina/imunologia , Neurotensina/metabolismo , Neurotransmissores/metabolismo , Distribuição TecidualAssuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Capsaicina/uso terapêutico , Irritantes/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Capsaicina/farmacologia , Fármacos Gastrointestinais/farmacologia , Fármacos Gastrointestinais/uso terapêutico , Cardiopatias/prevenção & controle , Humanos , Irritantes/farmacologia , Descongestionantes Nasais/farmacologia , Descongestionantes Nasais/uso terapêutico , Neoplasias/prevenção & controle , Doenças do Sistema Nervoso/tratamento farmacológicoRESUMO
The activation of monocytes/macrophages by several stimuli is an initial event in the inflammatory response. To ascertain the importance of LTB(4) and 5-lypoxigenase in the inflammatory site, we isolated and stimulated rat adherent granuloma macrophages (RAGMs) with calcium ionophore in the presence or absence of regulated on activation, normal T expressed and secreted (RANTES) [CCL5] at different concentrations. We tested the hypothesis that RANTES may influence the production of LTB(4) stimulated by calcium ionophore A23187 (2.5 microM/ml) in rat adherent granuloma macrophages derived from granuloma induced by potassium permanganate diluted 1:40 saturated solution. To test this hypothesis, we measured LTB(4) production, in rat granuloma macrophages stimulated with A23187 (2.5 microM) alone and in combination with RANTES at different concentrations. In these studies, the cell-free supernatant of stimulated RAGMs with the ionophore A23187, resulted in a drastic increase of LTB(4). However, when the cells were treated with the combination RANTES plus A23187 the stimulatory effect was more pronounced than A23187 alone. LTB(4) production was quantitated. The calcium ionophore A23187 directly induced LTB(4) in macrophages, this production was markedly enhanced when the cells were pretreated with RANTES. However, the addition of RANTES in the absence of calcium ionophore A23187 did not directly induce LTB(4) release, nor was lypoxigenase expression augmented. Preincubation of RAGMs with NDGA (nordihydroguiaretic acid) (10(-5)M) completely abolished the production of LTB4 on RAGMSs challenged with A23187 in combination with RANTES or A23187 alone in the supernatants. Similar effects were obtained when the cells were pretreated with dexamethasone. These data suggest, for the first time, that RANTES may stimulate the release of LTB(4), only when it is associated to other stimuli and for this reason we conclude that RANTES modulates inflammatory diseases, and may require other stimuli to be effective in amplifying its spectrum of action(s).
Assuntos
Calcimicina/farmacologia , Quimiocina CCL5/farmacologia , Granuloma/metabolismo , Leucotrieno B4/biossíntese , Macrófagos/metabolismo , Masoprocol/farmacologia , Permanganato de Potássio/toxicidade , Animais , Araquidonato 5-Lipoxigenase/genética , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Granuloma/induzido quimicamente , Masculino , RNA Mensageiro/análise , Ratos , Ratos WistarRESUMO
Apoptosis or programmed cell death is a physiological mechanism, characterized by specific morphological and biochemical changes such as cell shrinkage, chromatin condensation, protein cleavage, DNA breakdown and phagocytosis. Apoptosis is a significant contributor to the morphologic and functional development of multicellular organisms. It is also involved in the pathogenesis of several diseases including degenerative diseases of the central nervous system (CNS) like Alzheimer's disease or Parkinson's disease, cancer and immune system dysfunction. There are many factors, mainly proteins, which are involved in the activation, regulation and execution of related events. A fairly detailed outline of apoptotic mechanisms has also started to emerge and to be verified. In this short, focused mini-review, we attempt to outline current evidence regarding the mechanisms and the regulation of apoptosis.