EFFECTS OF SECRETOGRANIN II-DERIVED PEPTIDES ON THE RELEASE OF NEUROTRANSMITTERS MONITORED IN THE BASAL GANGLIA OF THE RAT WITH IN-VIVO MICRODIALYSIS

In vivo microdialysis was used to study the effect of secretogranin II -derived peptides on dynorphin B (Dyn B), dopamine, gamma-aminobutyric acid (GABA), glutamate and aspartate release in the substantia nigra and neostriatum of halothane-anaesthesized rats. In the substantia nig ra, local infusion of secretoneurin (secretogranin II 154-186) (1-50 m u M) increased, in a concentration-dependent manner, extracellular asp artate, glutamate, Dyn B, dopamine and GABA levels. The effect was par ticularly prominent on aspartate and glutamate levels which, following 50 mu M of secretoneurin, were increased by >20 and >10 fold, respect ively. However, the effect of secretoneurin on Dyn B release appeared to be more specific, since a significant increase (>2 fold) was alread y observed following 1 mu M of secretoneurin. In the neostriatum, Dyn B, glutamate, aspartate and GABA levels were also increased by local s ecretoneurin infusion, but the effect was less prominent than in the s ubstantia nigra. In the substantia nigra, only Dyn B levels were signi ficantly increased following infusion of 10 mu M of the secretoneurin- C terminal (secretoneurin-15C), whereas Dyn B and GABA levels were inc reased by the same concentration of the secretogranin II C terminus (Y M). Only glutamate and aspartate levels were increased by local infusi on of 10 mu M of secretogranin LT 133-151 (LF), a peptide adjacent to secretoneurin in the primary amino acid sequence. In the neostriatum, Dyn B and GABA levels were increased by 10 mu M of secretoneurin-15C. Dyn B levels were also increased by 10 mu M of YM, and glutamate and a spartate levels were increased by 10 mu M of both YM and LF. Thus, sec retogranin II-derived peptides affect extracellular levels of several putative neurotransmitter systems monitored in the basal ganglia of th e rat with in vivo microdialysis. The effect of Dyn B appears to be sp ecific and related to a physiological role of secretoneurin, since (i) it occurs in an area where secretoneurin-immunocytochemistry has been observed, (ii) is exerted at comparatively low concentrations, and (i ii) is mimicked by secretoneurin-15C. The increases in excitatory amin o acid levels produced by high concentrations of secretoneurin and oth er secretogranin II-derived peptides reflect, perhaps, a potential neu rotoxicity produced by abnormal accumulation of these peptides.