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外文期刊>european journal of neuroscience
>Alterations of G‐protein Coupling Function in Phosphoinositide Signalling Pathways of Rat Hippocampus by Ischaemic Brain Injury
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Alterations of G‐protein Coupling Function in Phosphoinositide Signalling Pathways of Rat Hippocampus by Ischaemic Brain Injury
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机译:Alterations of G‐protein Coupling Function in Phosphoinositide Signalling Pathways of Rat Hippocampus by Ischaemic Brain Injury
AbstractThe activation of membrane‐associated phospholipase C is rapidly and transiently induced in the central nervous system by a variety of stimuli. Ischaemic brain injury is one of the situations that leads to a dramatic increase in polyphosphoinositide (PPI) turnover. In this study, stimulation of PPI hydrolysis by glutamate (500 μM) was measured in hippocampal slices from rats up to 21 days after an ischaemic insult of 30 min. Ischaemia was induced using the four‐vessel occlusion method. PPI hydrolysis elicited by glutamate was significantly increased in the slices prepared from ischaemic rats 24 h after reperfusion, the accumulation of inositol phosphates (InsPs) and inositol 1,4,5‐trisphosphate (InsP3) was 614±74 (n= 8) and 182±11 (n= 9) of the basal level respectively. This potentiation was also observed 21 days after ischaemia. Hyper‐responsiveness to glutamate was also accompanied by an increase in AIF−4‐stimulated formation of 3Hinositol phosphates. In addition, global ischaemia did not change either high‐affinity 3Hglutamate binding in hippocampal membranes or the stimulation of PPI hydrolysis by carbachol or noradrenaline in hippocampal slices. The present results suggest that the increased responsiveness to glutamate is the result, at least in part, of functional changes at the G‐protein level, and may contribute to the pathophysiology of ischaemic brain injury or to the regenerative phenomena that accompan
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