期刊
JOURNAL OF NEUROCHEMISTRY
卷 98, 期 2, 页码 481-494出版社
WILEY
DOI: 10.1111/j.1471-4159.2006.03901.x
关键词
confocal imaging; dopamine receptors; presynaptic; rat striatum
资金
- NIA NIH HHS [AG21586] Funding Source: Medline
We have directly observed the effects of activating presynaptic D-1-like and D-2-like dopamine receptors on Ca2+ levels in isolated nerve terminals (synaptosomes) from rat striatum. R-(+)-SKF81297, a selective D-1-like receptor agonist, and (-)-quinpirole, a selective D-2-like receptor agonist, induced increases in Ca2+ levels in different subsets of individual striatal synaptosomes. The SKF81297- and quinpirole-induced effects were blocked by R-(+)-SCH23390, a D-1-like receptor antagonist, and (-)-sulpiride, a D-2-like receptor antagonist, respectively. SKF81297- or quinpirole-induced Ca2+ increases were inhibited following blockade of voltage-gated calcium channels or sodium channels. In a larger subset of synaptosomes, quinpirole decreased baseline Ca2+. Quinpirole also inhibited veratridine-induced increases in intrasynaptosomal Ca2+ level. Immunostaining confirmed the presynaptic expression of D-1, D-5, D-2 and D-3 receptors, but not D-4 receptors. The array of neurotransmitter phenotypes of the striatal nerve endings expressing D-1, D-5, D-2 or D-3 varied for each receptor subtype. These results suggest that presynaptic D-1-like and D-2-like receptors induce increases in Ca2+ levels in different subsets of nerve terminals via Na+ channel-mediated membrane depolarization, which, in turn, induces the opening of voltage-gated calcium channels. D-2-like receptors also reduce nerve terminal Ca2+ in a different but larger subset of synaptosomes, consistent with the predominant presynaptic action of dopamine in the striatum being inhibitory.
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