| Autor: |
Kemel, Marie-Louise, Perez, Sylvie, Beaujouan, Jean-Claude, Jabourian, Maritza, Soubrie, Philippe, Glowinski, Jacques |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; 10/15/2003, Vol. 87 Issue 2, p487, 10p |
| Abstrakt: |
Abstract Using an in vitro microsuperfusion procedure, the NMDA-evoked release of [[sup 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[sub 1] ) receptor antagonists and the ability of appropriate agonists to counteract the antagonist responses were investigated to determine whether tachykinin NK[sub 1] classic, septide-sensitive and/or new NK[sub 1] -sensitive receptors mediate these regulations. The NK[sub 1] antagonists, SR140333, SSR240600, GR205171 but not GR82334 and RP67580 (0.1 and 1 µm) markedly reduced the NMDA (1 mm + d-serine 10 µm)-evoked release of [[sup 3] H]ACh only in the matrix. These responses unchanged by coapplication with NMDA of NK[sub 2] or NK[sub 3] agonists, [Lys[sup 5] ,MeLeu[sup 9] ,Nle[sup 10] ]NKA(4–10) or senktide, respectively, were completely counteracted by the selective NK[sub 1] agonist, [Pro[sup 9] ]substance P but also by neurokinin A and neuropeptide K (1 nm each). According to the rank order of potency of agonists for counteracting the antagonist responses ([Pro[sup 9] ]substance P, 0.013 nm > neurokinin A, 0.15 nm > substance P(6–11) 7.7 nm = septide 8.7 nm), the new NK[sub 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[sub 1] antagonists having a high affinity for these receptors could be used as indirect anti-cholinergic agents. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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