PMID: 7521733Jan 1, 1993Paper

Substance P regulation of glutamate and cystine transport in human astrocytoma cells

Receptors & Channels
C L Johnson, C G Johnson

Abstract

UC11 human astrocytoma cells transported glutamate by at least two distinct systems which appeared to be very similar to the Na(+)-dependent XAG- system (glutamate and aspartate are preferred substrates) and the Na(+)-independent xc- system (glutamate and cystine are preferred substrates) described in other cells, including primary cultures of rat astrocytes. The xc- system accounted for about 80% of the total glutamate influx. In a Na(+)-free buffer, the average Km and Vmax values for glutamate influx in UC11 cells were 167 +/- 15 microM and 0.82 +/- 0.04 nmoles/min/mg protein. Substance P, acting via an NK1 receptor, caused half maximal inhibition of glutamate and cystine transport at a peptide concentration of approximately 3 nM. Maximal inhibition was usually in the range of 60-80% and was noncompetitive in nature. Substance P also induced a significant increase in the release of endogenous glutamate. These effects of Substance P may be of pathophysiological significance in the CNS: first, a combination of inhibition of glutamate influx and stimulation of glutamate efflux from astrocytes is potentially toxic with respect to nearby neurons; second, an inhibition of cystine influx could result in a depletion of intracellular ...Continue Reading

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