{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T20:18:22Z","timestamp":1768681102307,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"2b","license":[{"start":{"date-parts":[[2011,8,28]],"date-time":"2011-08-28T00:00:00Z","timestamp":1314489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,9,2]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>Sigma\u20101 receptors are atypical receptors with potentially two transmembrane domains. Antagonists require doses significantly higher than their published affinities to have biological effects. We have reassessed the binding characteristics of these ligands and found antagonists bind to high\u2010 and low\u2010affinity states not distinguished by agonists.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>The affinities of sigma\u20101 receptor ligands was assessed using radioligand saturation and competition binding of [<jats:sup>3<\/jats:sup>H]\u2010(+)\u2010pentazocine to permeabilized MDA\u2010MB\u2010468 cells. This was compared with the effect of ligands on metabolic activity using an MTS\u2010based assay and calcium signalling using cells loaded with the calcium dye, Fura\u20102.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>Sigma\u20101 receptor antagonists, but not agonists, show GTP\u2010 and suramin\u2010sensitive high\u2010affinity binding. Functional responses (calcium signalling and metabolic activity), while associated with sigma\u20101 receptor binding, required binding to an unidentified, low\u2010affinity target.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>Sigma\u20101 receptors are coupled to G proteins. This interaction is only observed when analysing antagonist binding. The identity of the G protein remains to be resolved. The concept of agonist and antagonist at the sigma\u20101 receptor needs to be revisited.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01417.x","type":"journal-article","created":{"date-parts":[[2011,4,12]],"date-time":"2011-04-12T10:32:35Z","timestamp":1302604355000},"page":"772-780","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Antagonists show GTP\u2010sensitive high\u2010affinity binding to the sigma\u20101 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