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An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine? 总被引:5,自引:0,他引:5
It has been proposed that three major receptor subtypes subserve the putative transmitter role of glutamate and aspartate in the mammalian central nervous system. One subtype is classified by the specific agonist N-methylaspartate (NMA) and the specific antagonist 4-amino-2-phosphonovaleric acid. It has been shown recently that excitation of neurones by NMA is also selectively reduced by dissociative anaesthetics such as ketamine and phencyclidine and by sigma opiates, drugs of abuse with common psychotomimetic properties. Responses to NMA have an unusual voltage relation which may result from a voltage-dependent block of the activated channel by physiological concentrations of magnesium. No synaptic potential with properties similar to those of responses to NMA, however, has yet been reported. We describe here an excitatory postsynaptic potential (e.p.s.p.) evoked by electrical stimulation of the white matter and recorded intracellularly from pyramidal cells in slices of rat somatosensory cortex. This e.p.s.p. has the appropriate voltage relation and sensitivity to Mg2+ and ketamine to be an NMA receptor-mediated synapse and a potential central site for the psychotomimetic actions of ketamine. 相似文献
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The endoplasmic reticulum is the principal site of synthesis and initial incorporation of membrane lipids in eukaryotic cells; the enzymes of glycerolipid biosynthesis are exclusively located on its cytoplasmic surface. To maintain a phospholipid bilayer in this organelle, newly synthesized phospholipids must be translocated to the lumenal surface. Consistent with this are measurements indicating that movement of phospholipids across microsomal membranes is rapid, with a half-time less than 5 min (refs 3 and 4). Rapid movement of phospholipids has also been detected across the plasma membrane of Bacillus megaterium, another site of de novo lipid biosynthesis. The rapid transmembrane movement of phosphatidylcholine has not been detected, however, in vesicles prepared from microsomal lipids. These latter data suggest involvement in the endoplasmic reticulum of a phospholipid-translocating protein, as was first proposed by Bretscher who called it 'flippase'. Here we report reconstitution of a phospholipid flippase from rat liver microsomes into lipid vesicles. 相似文献
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A L Demain 《Nature》1966,212(5057):93-94
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A functional correlate for the dihydropyridine binding site in rat brain 总被引:11,自引:0,他引:11
Calcium channels, controlling the influx of extracellular Ca2+ and hence neurotransmitter release, exist in the brain. However, drugs classed as calcium antagonists and which inhibit Ca2+ entry through voltage-activated Ca2+ channels in heart and smooth muscle, seem not to affect any aspect of neuronal function in the brain at pharmacologically relevant concentrations. Yet the dihydropyridine calcium antagonists (for example, nitrendipine) bind stereospecifically with high affinity to a recognition site on brain-cell membranes thought to represent the Ca2+ channel and consequently, the physiological relevance of these sites has been questioned. However, activation of voltage-dependent Ca2+ channels can increase cytoplasmic Ca2+ and neurotransmitter release in neuronal tissue. We show here that Bay K8644, a dihydropyridine Ca2+-channel activator, can augment K+-stimulated release of serotonin from rat frontal cortex slices and that these effects can be antagonized by low concentrations of calcium antagonists. As 3H-dihydropyridine binding to cortical membrane preparations resembles the binding in heart and smooth muscle where there are good functional correlates we conclude that the dihydropyridine binding sites in the brain represent functional Ca2+ channels that can be unmasked under certain circumstances. 相似文献
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Trypsin immobilised on polystyrene beads causes initiation of cell division which cannot be accounted for by trypsin released into the medium or into the cells. Also, initiation by soluble trypsin is inhibited by immobilised soybean trypsin inhibitor. These results demonstrate that trypsin can initiate proliferation at the cell surface. 相似文献