Distinct regulations by septide and the neurokinin-1 tachykinin receptor agonist [pro9]substance P of the N-methyl-D-aspartate-evoked release of dopamine in striosome- and matrix-enriched areas of the rat striatum.
The effects of septide (a short substance P C-terminal analogue) and of the neurokinin-1 receptor agonist [Pro9]substance P on the N-methyl-D-aspartate (50 microM)-evoked release of [3H]dopamine (continuously synthesized from [3H]tyrosine) were investigated in the absence or the presence of the selective neurokinin-1 receptor antagonist RP 67580 in selected striosome- and matrix-enriched areas of the rat striatum. Experiments were performed in vitro using a microsuperfusion procedure described previously. At a concentration of 0.1 microM, septide and [Pro9]substance P stimulated the spontaneous release of [3H]dopamine in striosome-enriched areas similarly. However, in this compartment, these peptides induced larger and opposite effects on the N-methyl-D-aspartate (50 microM)-evoked release of [3H]dopamine (estimated in the absence of magnesium). Indeed, septide markedly enhanced the N-methyl-D-aspartate response, while [Pro9]substance P largely reduced the N-methyl-D-aspartate-evoked release of [3H]dopamine. Septide also enhanced the N-methyl-D-aspartate response in the matrix, but [Pro9]substance P was without effect. When used alone, at 0.1 or 1 microM, RP 67580 reduced by about 33% the N-methyl-D-aspartate-evoked release of [3H]dopamine in striosome-enriched areas. In contrast, in the matrix, the N-methyl-D-aspartate response was enhanced in the presence of a low concentration of the antagonist, while the higher concentration was ineffective. In striosomes, the reducing effect of [Pro9]substance P and the enhancing action of septide on the N-methyl-D-aspartate response were respectively blocked in the presence of low and high concentrations of RP 67580, while the stimulatory effect of septide on the N-methyl-D-aspartate response in the matrix was prevented with both concentrations of the neurokinin-1 receptor antagonist. Finally, the co-application of [Pro9]substance P (0.1 microM) with septide (0.1 microM) abolished the enhancing effect of septide on the N-methyl-D-aspartate-evoked release of [3H]dopamine in both striatal compartments. Altogether, these results suggest that substance P and eventually one of its metabolites, substance P(6-11) or another endogenous tachykinin released under the action of N-methyl-D-aspartate, contribute to the regulation of [3H]dopamine release in both striatal compartments. They also extend previous observations which allowed us to demonstrate that the local circuits contributing to the presynaptic regulation of [3H]dopamine release differ in striosome- and matrix-enriched areas. Furthermore, in agreement with observations made in some peripheral tissues, the present results support the existence of "septide-sensitive" tachykinin receptors in the rat striatum or alternatively of septide sensitive sites on tachykinin neurokinin-1 receptors distinct from those sensitive to neurokinin-1 receptor agonists, coupled to distinct transducing systems, and thus leading to biological responses which differ from those evoked by neurokinin-1 receptor agonists.
Gauchy
C
C
Chaire de Neuropharmacologie, INSERM U114, Collège de France, Paris, France.
Desban
M
M
Glowinski
J
J
Kemel
M L
ML
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D007211:Indoles; D054833:Isoindoles; D010446:Peptide Fragments; D018039:Receptors, Tachykinin; C067285:substance P, Pro(9)-; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D016202:N-Methylaspartate; C054725:septide; D011761:Pyrrolidonecarboxylic Acid; D004298:Dopamine