DISTINCT REGULATIONS BY SEPTIDE AND THE NEUROKININ-1 TACHYKININ RECEPTOR AGONIST [PRO(9)]SUBSTANCE-P OF THE N-METHYL-D-ASPARTATE-EVOKED RELEASE OF DOPAMINE IN STRIOSOME-ENRICHED AND MATRIX-ENRICHED AREAS OF THE RAT STRIATUM
C. Gauchy et al., DISTINCT REGULATIONS BY SEPTIDE AND THE NEUROKININ-1 TACHYKININ RECEPTOR AGONIST [PRO(9)]SUBSTANCE-P OF THE N-METHYL-D-ASPARTATE-EVOKED RELEASE OF DOPAMINE IN STRIOSOME-ENRICHED AND MATRIX-ENRICHED AREAS OF THE RAT STRIATUM, Neuroscience, 73(4), 1996, pp. 929-939
The effects of septide (a short substance P C-terminal analogue) and o
f the neurokinin-1 receptor agonist [Pro(9)]substance P on the N-methy
l-D-aspartate (50 mu M)-evoked release of [H-3]dopamine (continuously
synthesized from [H-3]tyrosine) were investigated in the absence or th
e 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 mu M, septide and [Pr
o(9)]substance P stimulated the spontaneous release of [H-3]dopamine i
n striosome-enriched areas similarly. However, in this compartment, th
ese peptides induced larger and opposite effects on the N-methyl-D-asp
artate (50 mu M)-evoked release of [H-3]dopamine (estimated in the abs
ence of magnesium). Indeed, septide markedly enhanced the N-methyl-D-a
spartate response, while [Pro(9)]substance P largely reduced the N-met
hyl-D-aspartate-evoked release of [H-3]dopamine. Septide also enhanced
the N-methyl-D-aspartate response in the matrix, but [Pro(9)]substanc
e P was without effect. When used alone, at 0.1 or 1 mu M, RP 67580 re
duced by about 33% the N-methyl-D-aspartate-evoked release of [H-3]dop
amine in striosome-enriched areas. In contrast, in the matrix, the N-m
ethyl-D-aspartate response was enhanced in the presence of a low conce
ntration of the antagonist, while the higher concentration was ineffec
tive. In striosomes, the reducing effect of [Pro(9)]substance P and th
e enhancing action of septide on the N-methyl-D-aspartate response wer
e 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 concentratio
ns of the neurokinin-1 receptor antagonist. Finally, the co-applicatio
n of [Pro(9)]substance P (0.1 mu M) with septide (0.1 mu M) abolished
the enhancing effect of septide on the N-methyl-D-aspartate-evoked rel
ease of [H-3]dopamine in both striatal compartments. Altogether, these
results suggest that substance P and eventually one of its metabolite
s, substance P(6-11) or another endogenous tachykinin released under t
he action of N-methyl-D-aspartate, contribute to the regulation of [H-
3]dopamine release in both striatal compartments. They also extend pre
vious observations which allowed us to demonstrate that the local circ
uits contributing to the presynaptic regulation of [H-3]dopamine relea
se differ in striosome- and matrix-enriched areas. Furthermore, in agr
eement with observations made in some peripheral tissues, the present
results support the existence of ''septide-sensitive'' tachykinin rece
ptors 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 system
s, and thus leading to biological responses which differ from those ev
oked by neurokinin-1 receptor agonists. Copyright (C) 1996 IBRO.