title: Facilitation by endogenous tachykinins of the NMDA-evoked release of acetylcholine after acute and chronic suppression of dopaminergic transmission in the matrix of the rat striatum.
abstract: Using a microsuperfusion method in vitro, the effects of the NK1, NK2, and NK3 tachykinin receptor antagonists SR140333, SR48968, and SR142801, respectively, on the NMDA-evoked release of [3H]-acetylcholine were investigated after both acute and chronic suppression of dopamine transmission in striosomes and matrix of the rat striatum. NMDA (1 mm) alone or with D-serine (10 microm) in the presence of alpha-methyl-p-tyrosine (100 microm) markedly enhanced the release of [3H]-acetylcholine through a dopamine-independent inhibitory process. In both conditions, as well as after chronic 6-OHDA-induced denervation of striatal dopaminergic fibers, SR140333, SR48968, or SR142801 (0.1 microm each) reduced the NMDA-evoked release of [3H]-acetylcholine in the matrix but not in striosome-enriched areas. These responses were selectively abolished by coapplication with NMDA of the respective tachykinin agonists, septide, [Lys5,MeLeu9,Nle10]NKA(4-10), or senktide. Distinct mechanisms are involved in the effects of the tachykinin antagonists because the inhibitory response of SR140333 was additive with that of either SR48968 or SR142801. In addition, the SR140333-evoked response remained unchanged, whereas those of SR48968 and SR142801 were abolished in the presence of N(G)-monomethyl-l-arginine (nitric oxide synthase inhibitor). Therefore, in the matrix but not in striosomes, the acute or chronic suppression of dopamine transmission unmasked the facilitatory effects of endogenously released substance P, neurokinin A, and neurokinin B on the NMDA-evoked release of [3H]-acetylcholine. Whereas substance P and neurokinin A are colocalized in same efferent neurons, their responses involve distinct circuits because the substance P response seems to be mediated by NK1 receptors located on cholinergic interneurons, while those of neurokinin A and neurokinin B are nitric oxide-dependent.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U114, Collège de France, 75231 Paris, France. marie-lou.kemel@collège-de-france.fr
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Kemel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pérez
authors.forename: Gérard
authors.initials: G
authors.lastname: Godeheu
authors.forename: Philippe
authors.initials: P
authors.lastname: Soubrié
authors.forename: Jacques
authors.initials: J
authors.lastname: Glowinski
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015320:Tachykinins / Q000819:agonists / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001549:Benzamides; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010880:Piperidines; D011812:Quinuclidines; D018039:Receptors, Tachykinin; D015320:Tachykinins; C054724:senktide; C085215:SR 140333; D013373:Substance P; D016202:N-Methylaspartate; C073839:SR 48968; C054725:septide; D016627:Oxidopamine; C091554:SR 142801; D000109:Acetylcholine; D011761:Pyrrolidonecarboxylic Acid; D004298:Dopamine