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The new neurokinin 1‐sensitive receptor mediates the facilitation by endogenous tachykinins of the NMDA‐evoked release of acetylcholine after suppression of dopaminergic transmission in the matrix of the rat striatum
Author(s) -
Kemel MarieLouise,
Pérez Sylvie,
Beaujouan JeanClaude,
Jabourian Maritza,
Soubrié Philippe,
Glowinski Jacques
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02010.x
Subject(s) - dopaminergic , facilitation , acetylcholine , striatum , neuroscience , nmda receptor , neurokinin a , chemistry , endogeny , neurotransmission , dopamine , receptor , pharmacology , substance p , medicine , psychology , neuropeptide , biochemistry
Using an in vitro microsuperfusion procedure, the NMDA‐evoked release of [ 3 H]ACh was studied after suppression of dopamine (DA) transmission (α‐methyl‐ p ‐tyrosine) in striatal compartments of the rat. The effects of tachykinin neurokinin 1 (NK 1 ) receptor antagonists and the ability of appropriate agonists to counteract the antagonist responses were investigated to determine whether tachykinin NK 1 classic, septide‐sensitive and/or new NK 1 ‐sensitive receptors mediate these regulations. The NK 1 antagonists, SR140333, SSR240600, GR205171 but not GR82334 and RP67580 (0.1 and 1 µ m ) markedly reduced the NMDA (1 m m + d ‐serine 10 µ m )‐evoked release of [ 3 H]ACh only in the matrix. These responses unchanged by coapplication with NMDA of NK 2 or NK 3 agonists, [Lys 5 ,MeLeu 9 ,Nle 10 ]NKA(4–10) or senktide, respectively, were completely counteracted by the selective NK 1 agonist, [Pro 9 ]substance P but also by neurokinin A and neuropeptide K (1 n m each). According to the rank order of potency of agonists for counteracting the antagonist responses ([Pro 9 ]substance P, 0.013 n m > neurokinin A, 0.15 n m ≫ substance P(6–11) 7.7 n m = septide 8.7 n m ), the new NK 1 ‐sensitive receptors mediate the facilitation by endogenous tachykinins of the NMDA‐evoked release of ACh in the matrix, after suppression of DA transmission. Solely the NK 1 antagonists having a high affinity for these receptors could be used as indirect anti‐cholinergic agents.