Abstract

The characteristics of release of amino acids evoked by substance P from the neonatal rat spinal cord were examined. A hemisected spinal cord was continuously perfused and the release of amino acids into the perfusate was measured using high-performance liquid chromatography with a precolumn derivatization technique. Substance P (10 microM) evoked a significant increase in the release of aspartate, glutamate, GABA, glycine and taurine. The substance P-evoked release of these five amino acids was not reduced by Ca(2+)-free medium, but was blocked by [D-Pro4,D-Trp] substance P4-11 (10 microM). Perfusion of the spinal cord with low-Na+ medium (22 mM) induced a marked increase in the high-K+ (90mM)-evoked release of GABA, glutamate and glycine. In contrast, the substance P-evoked release of the five amino acids was significantly decreased by the low-Na+ medium. Similarly, perfusion of the spinal cord with low-Cl- medium (8 mM) increased the high-K(+)-evoked release of GABA and glycine, but decreased the substance P-evoked release of GABA, glycine and taurine. The substance P-evoked release of the five amino acids was dose-dependently blocked by d-tubocurarine (3-10 microM), whereas it was not blocked by tetrodotoxin (0.2 microM) or amiloride (30 microM). Compound 48/80 (10 micrograms/ml), a histamine-releasing agent on mast cells, evoked release of the amino acids from the spinal cord with characteristics similar to those of substance P-evoked amino acid release.(ABSTRACT TRUNCATED AT 250 WORDS)

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