title: Substance P regulation of glutamate and cystine transport in human astrocytoma cells.
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 glutathione, resulting in increased sensitivity to oxidative stress.
authors.affiliation: Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0575.
authors.forename: C L
authors.initials: CL
authors.lastname: Johnson
authors.forename: C G
authors.initials: CG
authors.lastname: Johnson
mesh_terms: D001254:Astrocytoma / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D003553:Cystine / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006801:Humans; D007700:Kinetics; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D005971:Glutamates; D018040:Receptors, Neurokinin-1; D013373:Substance P; D018698:Glutamic Acid; D003553:Cystine; D012964:Sodium