Inhibitory effects of GABA, L-glutamic acid and nicotine on the potassium-evoked release of subsaance P in substantia nigra slices of the rat

Abstract

Rat substantia nigra slices were superfused with a physiological medium containing a diluted substance P (SP) antiserum, bacitracin and serum albumin to measure SP released in superfusates. As shown by measuring the degradation of a SP-labelled derivative incubated with cerebellar slices, this medium prevented the enzymatic inactivation of SP. Potassium (K +, 50 mM) and veratridine (5 × 10 −5M) stimulated SP release and these effects were respectively prevented in absence of calcium and in presence of tetrodotoxin (5 × 10 −7 M). GABA (5 × 10 −5 M) nicotine (10 −6 M) and L-glutamic acid (5 × 10 −5 M) reduced the K + (50 mM)-evoked release of SP. In contrast, glycine (5 × 10 −5 M), oxotremorine (5 × 10 −5 M), D-glutamic acid (5 × 10 −5 M) and serotonin (5 × 10 −5 M) were without effect. Pempidine (10 − M) prevented the inhibitory effect of nicotine (10 − M) on the K +-evoked release of SP. Glutamic acid diethyl ester (10 −4 M) completely abolished the L-glutamic acid-induced inhibition of the K +-evoked release of SP. Picrotoxin (5 × 10 −5 M) did not influence the L-glutamic acid inhibitory effect excluding the intervention of GABAergic mechanisms.