pubmed-article:10212487 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C0205101 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C0028351 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C0015283 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C0086376 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C0031669 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C1948023 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C0051404 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C1817828 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C0596235 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C1546857 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C0127400 | lld:lifeskim |
pubmed-article:10212487 | lifeskim:mentions | umls-concept:C0051403 | lld:lifeskim |
pubmed-article:10212487 | pubmed:issue | 1381 | lld:pubmed |
pubmed-article:10212487 | pubmed:dateCreated | 1999-5-27 | lld:pubmed |
pubmed-article:10212487 | pubmed:abstractText | alpha-latrotoxin (LTX) stimulates massive release of neurotransmitters by binding to a heptahelical transmembrane protein, latrophilin. Our experiments demonstrate that latrophilin is a G-protein-coupled receptor that specifically associates with heterotrimeric G proteins. The latrophilin-G protein complex is very stable in the presence of GDP but dissociates when incubated with GTP, suggesting a functional interaction. As revealed by immunostaining, latrophilin interacts with G alpha q/11 and G alpha o but not with G alpha s, G alpha i or G alpha z, indicating that this receptor may couple to several G proteins but it is not promiscuous. The mechanisms underlying LTX-evoked norepinephrine secretion from rat brain nerve terminals were also studied. In the presence of extracellular Ca2+, LTX triggers vesicular exocytosis because botulinum neurotoxins E, Cl or tetanus toxin inhibit the Ca(2+)-dependent component of the toxin-evoked release. Based on (i) the known involvement of G alpha q in the regulation of inositol-1,4,5-triphosphate generation and (ii) the requirement for Ca2+ in LTX action, we tested the effect of inhibitors of Ca2+ mobilization on the toxin-evoked norepinephrine release. It was found that aminosteroid U73122, which inhibits the coupling of G proteins to phospholipase C, blocks the Ca(2+)-dependent toxin's action. Thapsigargin, which depletes intracellular Ca2+ stores, also potently decreases the effect of LTX in the presence of extracellular Ca2+. On the other hand, clostridial neurotoxins or drugs interfering with Ca2+ metabolism do not inhibit the Ca2(+)-independent component of LTX-stimulated release. In the absence of Ca2+, the toxin induces in the presynaptic membrane non-selective pores permeable to small fluorescent dyes; these pores may allow efflux of neurotransmitters from the cytoplasm. Our results suggest that LTX stimulates norepinephrine exocytosis only in the presence of external Ca2+ provided intracellular Ca2+ stores are unperturbed and that latrophilin, G proteins and phospholipase C may mediate the mobilization of stored Ca2+, which then triggers secretion. | lld:pubmed |
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pubmed-article:10212487 | pubmed:language | eng | lld:pubmed |
pubmed-article:10212487 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:10212487 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:10212487 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:10212487 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:10212487 | pubmed:month | Feb | lld:pubmed |
pubmed-article:10212487 | pubmed:issn | 0962-8436 | lld:pubmed |
pubmed-article:10212487 | pubmed:author | pubmed-author:DollyJ OJO | lld:pubmed |
pubmed-article:10212487 | pubmed:author | pubmed-author:RahmanM AMA | lld:pubmed |
pubmed-article:10212487 | pubmed:author | pubmed-author:UshkaryovY... | lld:pubmed |
pubmed-article:10212487 | pubmed:author | pubmed-author:AshtonA CAC | lld:pubmed |
pubmed-article:10212487 | pubmed:author | pubmed-author:DavletovB ABA | lld:pubmed |
pubmed-article:10212487 | pubmed:author | pubmed-author:MeunierF AFA | lld:pubmed |
pubmed-article:10212487 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:10212487 | pubmed:day | 28 | lld:pubmed |
pubmed-article:10212487 | pubmed:volume | 354 | lld:pubmed |
pubmed-article:10212487 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:10212487 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:10212487 | pubmed:pagination | 379-86 | lld:pubmed |
pubmed-article:10212487 | pubmed:dateRevised | 2010-8-25 | lld:pubmed |
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pubmed-article:10212487 | pubmed:year | 1999 | lld:pubmed |
pubmed-article:10212487 | pubmed:articleTitle | Norepinephrine exocytosis stimulated by alpha-latrotoxin requires both external and stored Ca2+ and is mediated by latrophilin, G proteins and phospholipase C. | lld:pubmed |