{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:26:19Z","timestamp":1789230379058,"version":"build-2803163510"},"reference-count":46,"publisher":"The Royal Society","issue":"1381","license":[{"start":{"date-parts":[[1999,2,28]],"date-time":"1999-02-28T00:00:00Z","timestamp":920160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phil. Trans. R. Soc. Lond. B"],"published-print":{"date-parts":[[1999,2,28]]},"abstract":"<jats:p>\n                    \u03b1\u2013latrotoxin (LTX) stimulates massive release of neurotransmitters by binding to a heptahelical transmembrane protein, latrophilin. Our experiments demonstrate that latrophilin is a G\u2013protein\u2013coupled receptor that specifically associates with heterotrimeric G proteins. The latrophilin\u2013G 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\u03b1\n                    <jats:sub>q\/11<\/jats:sub>\n                    and G\u03b1\n                    <jats:sub>o<\/jats:sub>\n                    but not with G\u03b1\n                    <jats:sub>s<\/jats:sub>\n                    , G\u03b1\n                    <jats:sub>i<\/jats:sub>\n                    or G\u03b1\n                    <jats:sub>z<\/jats:sub>\n                    , indicating that this receptor may couple to several G proteins but it is not promiscuous. The mechanisms underlying LTX\u2013evoked norepinephrine secretion from rat brain nerve terminals were also studied. In the presence of extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , LTX triggers vesicular exocytosis because botulinum neurotoxins E, C1 or tetanus toxin inhibit the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2013dependent component of the toxin\u2013evoked release. Based on (i) the known involvement of G\u03b1\n                    <jats:sub>q<\/jats:sub>\n                    in the regulation of inositol\u20131,4,5\u2013triphosphate generation and (ii) the requirement of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    in LTX action, we tested the effect of inhibitors of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    mobilization on the toxin\u2013evoked norepinephrine release. It was found that aminosteroid U73122, which inhibits the coupling of G proteins to phospholipase C, blocks the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2013dependent toxin's action. Thapsigargin, which depletes intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    stores, also potently decreases the effect of LTX in the presence of extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    . On the other hand, clostridial neurotoxins or drugs interfering with Ca\n                    <jats:sup>2+<\/jats:sup>\n                    metabolism do not inhibit the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2013independent component of LTX\u2013stimulated release. In the absence of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , the toxin induces in the presynaptic membrane non\u2013selective 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 Ca\n                    <jats:sup>2+<\/jats:sup>\n                    provided intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    stores are unperturbed and that latrophilin, G proteins and phospholipase C may mediate the mobilization of stored Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , which then triggers secretion.\n                  <\/jats:p>","DOI":"10.1098\/rstb.1999.0390","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:55:21Z","timestamp":1027713321000},"page":"379-386","source":"Crossref","is-referenced-by-count":76,"title":["Norepinephrine exocytosis stimulated by \u03b1\u2013latrotoxin requires both external and stored Ca\n                    <sup>2+<\/sup>\n                    and is mediated by latrophilin, G proteins and phospholipase C"],"prefix":"10.1098","volume":"354","author":[{"given":"M. Atiqur","family":"Rahman","sequence":"first","affiliation":[{"name":"Biochemistry Department, Imperial College, Exhibition Road, London SW7 2AY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony C.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Imperial College, Exhibition Road, London SW7 2AY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric A.","family":"Meunier","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Imperial College, Exhibition Road, London SW7 2AY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bazbek A.","family":"Davletov","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Imperial College, Exhibition Road, London SW7 2AY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Oliver Dolly","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Imperial College, Exhibition Road, London SW7 2AY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri A.","family":"Ushkaryov","sequence":"additional","affiliation":[{"name":"Biochemistry Department, Imperial College, Exhibition Road, London SW7 2AY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[1999,2,28]]},"reference":[{"key":"p_1","doi-asserted-by":"crossref","unstructured":"Barnett D. 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Series B: Biological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.1999.0390","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rstb.1999.0390","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:26:19Z","timestamp":1778621179000},"score":1,"resource":{"primary":{"URL":"http:\/\/royalsocietypublishing.org\/rstb\/article\/354\/1381\/379-386\/19384"}},"subtitle":[],"editor":[{"given":"F.","family":"Clementi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"R.","family":"Fesce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"J.","family":"Meldolesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"F.","family":"Valtorta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[1999,2,28]]},"references-count":46,"journal-issue":{"issue":"1381","published-print":{"date-parts":[[1999,2,28]]}},"alternative-id":["10.1098\/rstb.1999.0390"],"URL":"https:\/\/doi.org\/10.1098\/rstb.1999.0390","relation":{},"ISSN":["0962-8436","1471-2970"],"issn-type":[{"value":"0962-8436","type":"print"},{"value":"1471-2970","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,2,28]]}}}