In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 23, No. 17 ( 2003-07-30), p. 6810-6818
Kurzfassung:
The effect of the human immunodeficiency virus-1 protein Tat was investigated on neurotransmitter release from human and rat cortical nerve endings. Tat failed to affect the release of several neurotransmitters, such as glutamate, GABA, norepinephrine, and others, but it evoked the release of [ 3 H]ACh via increase of cytosolic [Ca 2 + ]. In human nerve terminals, the Tat effect partly depends on Ca 2 + entry through voltage-sensitive Ca 2 + channels, because Cd 2 + halved the Tat-evoked release. Activation of group I metabotropic glutamate receptors (mGluR) and mobilization of Ca 2 + from IP 3 -sensitive intraterminal stores are also involved, because the Tat effect was prevented by mGluR antagonists 2-methyl-6-(phenylethynyl)pyridine hydrochloride and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester and by the IP 3 receptor antagonists heparin and xestospongin C. Furthermore, the group I selective mGlu agonist (RS)-3,5-dihydroxyphenylglycine enhanced [ 3 H]ACh release. In rat nerve terminals, the Tat-evoked release neither depends on external Ca 2 + ions entry nor on IP 3 -mediated mechanisms. Tat seems to cause mobilization of Ca 2 + from ryanodine-sensitive internal stores because its effect was prevented by both 8-bromo-cyclic adenosine diphosphate-ribose and dantrolene. The Tat-evoked release from human synaptosomes was mimicked by the peptide sequences Tat 32-62, Tat 49-86, and Tat 41-60. In contrast, the Tat 49-86 and Tat 61-80 fragments, but not the Tat 32-62 fragment, were active in rat synaptosomes. In conclusion, Tat elicits Ca 2 + -dependent [ 3 H]ACh release by species-specific intraterminal mechanisms by binding via discrete amino acid sequences to different receptive sites on human and rat cholinergic terminals.
Materialart:
Online-Ressource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.23-17-06810.2003
Sprache:
Englisch
Verlag:
Society for Neuroscience
Publikationsdatum:
2003
ZDB Id:
1475274-8
SSG:
12
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