Glutamate is acknowledged as an excitatory neurotransmitter in the vertebrate central nervous system (CNS). Glutamate is also postulated to play an important role in the pathogenesis of the neuronal cell loss that is associated with several neurological disease states in the CNS. Glutamate cytotoxicity in the cortical and retinal neurons in culture is mediated by nitric oxide (NO). As the excitatory action of glutamate is regulated by other neurotransmitters, the cytotoxic action of glutamate may be affected by other endogenous substances. We have used the term “neuroprotective factor” for endogenous substances having neuroprotective actions against glutamate cytotoxicity. We have previously found that cholecystokinin (CCK) prevented glutamate toxicity in the cortical neurons in culture. The evidence has suggested that CCKB-receptor stimulation causes suppression of a step in NO formation triggered by N-methyl-D-aspartate (NMDA) receptors. Nicotinic acetylcholine also protected cultured cortical neurons against NMDA receptor-mediated glutamate toxicity. In the cultured retinal neurons, dopamine prevented NMDA receptor-mediated glutamate cytotoxicity via D1-receptors. These substances may have a role to promote cell survival in the life-regulatory function of the CNS.
The greater curvature of the stomach of fasted rats was cut under urethane anesthesia (1.25 g/kg, i.p.). The dorsal side of the glandular stomach was fixed in a plastic chamber by facing the mucosal side to the chamber and perfused with warm Tyrode solution at 37°C. A window made by partial removal of the serosa, the muscularis externa and the submucosa allowed us to observe the basal part of the mucosal microcirculation through the muscularis mucosae. Images of the microcirculation were transmitted through a TV camera to a TV monitor screen and recorded on videotapes by a videotaperecorder. The diameters of the arterioles, collecting venules and venules were measured by an image analyzer. Arterioles, running along the muscularis mucosae, responded to acetylcholine and epinephrine applied on the window, by dilatation and constriction, respectively, but the collecting venules and venules showed no changes in diameter. Application of 50% ethanol on the mucosal side caused dilatation of the arterioles and constriction of the collecting venules and venules. This method may be useful for analyzing the mechanisms of gastric mucosal injury and those of the effects of vasoactive agents on the gastric mucosal microcirculation.