ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Using an in vitro microsuperfusion procedure, the NMDA-evoked release of [3H]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 (NK1) receptor antagonists and the ability of appropriate agonists to counteract the antagonist responses were investigated to determine whether tachykinin NK1 classic, septide-sensitive and/or new NK1-sensitive receptors mediate these regulations. The NK1 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 [3H]ACh only in the matrix. These responses unchanged by coapplication with NMDA of NK2 or NK3 agonists, [Lys5,MeLeu9,Nle10]NKA(4–10) or senktide, respectively, were completely counteracted by the selective NK1 agonist, [Pro9]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 ([Pro9]substance P, 0.013 nm 〉 neurokinin A, 0.15 nm ≫ substance P(6–11) 7.7 nm = septide 8.7 nm), the new NK1-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 NK1 antagonists having a high affinity for these receptors could be used as indirect anti-cholinergic agents.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.2003.02010.x
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