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Substance P-Evoked release of GABA from isolated spinal cord of the newborn rat

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DOI: 10.1016/0306-4522(91)90229-h


Abstract Isolated spinal cords of newborn rats were perfused with artificial cerebrospinal fluid and the effects of substance P and its analogs on the release of endogenous GABA were examined. Application of substance P evoked a dose-dependent release of GABA from spinal cords. The threshold concentration of substance P for induction of a significant increase in the GABA release was 3μM. The substance P-evoked GABA release was neither blocked by removal of Ca 2+ from perfusion medium nor by tetrodotoxin. In contrast, the GABA release evoked by high K + (90 mM) was abolished in Ca 2+ -free medium, and the GABA release evoked by veratridine (5μM) was suppressed by tetrodotoxin (1 μM). A GABA uptake inhibitor, cis-4-hydroxynipecotic acid, markedly augmented the GABA release induced by high K +, but not that induced by substance P or veratridine. These results suggest the possibility that a carrier-mediated mechanism might be involved in the GABA release induced by substance P, as well as by veratridine, in the newborn rat spinal cord. Two N-terminal fragments of substance P, substance P free acid and substance P 1–10 amide, as well as [ d-Arg 1, d-Trp 7,9,Leu 11]substance P (spantide), evoked an increase in the GABA release, whereas substance P 1–6 and a C-terminal fragment, substance P 5–11 were inactive. Somatostatin and compound 48/80 also evoked a GABA release, which was independent of external Ca 2+ and resistant to tetrodotoxin. [ d-Pro 4, d-Trp 7,9,10]substance P 4–11 (10–15 μM) inhibited the GABA release evoked by substance P, somatostatin and compound 48/80. These results showed that the features of the GABA release evoked by substance P, somatostatin and compound 48/80 from the neonatal rat spinal cord are similar to those of the histamine release evoked by these compounds from mast cells and suggest the involvement of a similar or the same mechanism in the releases from two tissues.

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