{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:46:39Z","timestamp":1792201599211,"version":"4.4.0"},"reference-count":51,"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>Muscarinic toxins (MTs) are snake venom peptides named for their ability to interfere with ligand binding to muscarinic acetylcholine receptors (mAChRs). Recent data infer that these toxins may have other G\u2010protein\u2010coupled receptor targets than the mAChRs. The purpose of this study was to systematically investigate the interactions of MTs with the adrenoceptor family members.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>We studied the interaction of four common MTs, MT1, MT3, MT7 and MT\u03b1, with cloned receptors expressed in insect cells by radioligand binding. Toxins showing modest to high\u2010affinity interactions with adrenoceptors were additionally tested for effects on functional receptor responses by way of inhibition of agonist\u2010induced Ca<jats:sup>2+<\/jats:sup>increases.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>All MTs behaved non\u2010competitively in radioligand displacement binding. MT1 displayed higher binding affinity for the human \u03b1<jats:sub>2B<\/jats:sub>\u2010adrenoceptor (IC<jats:sub>50<\/jats:sub>= 2.3\u2003nM) as compared with muscarinic receptors (IC<jats:sub>50<\/jats:sub>\u2265 100\u2003nM). MT3 appeared to have a broad spectrum of targets showing high\u2010affinity binding (IC<jats:sub>50<\/jats:sub>= 1\u201310\u2003nM) to M<jats:sub>4<\/jats:sub>mAChR, \u03b1<jats:sub>1A<\/jats:sub>\u2010, \u03b1<jats:sub>1D<\/jats:sub>\u2010 and \u03b1<jats:sub>2A<\/jats:sub>\u2010adrenoceptors and lower affinity binding (IC<jats:sub>50<\/jats:sub>\u2265 25\u2003nM) to \u03b1<jats:sub>1B<\/jats:sub>\u2010 and \u03b1<jats:sub>2C<\/jats:sub>\u2010adrenoceptors and M<jats:sub>1<\/jats:sub>mAChR. MT7 did not detectably bind to other receptors than M<jats:sub>1<\/jats:sub>, and MT\u03b1 was specific for the \u03b1<jats:sub>2B<\/jats:sub>\u2010adrenoceptor. None of the toxins showed effects on \u03b2<jats:sub>1<\/jats:sub>\u2010 or \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptors.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>Some of the MTs previously found to interact predominantly with mAChRs were shown to bind with high affinity to selected adrenoceptor subtypes. This renders these peptide toxins useful for engineering selective ligands to target various adrenoceptors.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01468.x","type":"journal-article","created":{"date-parts":[[2011,5,10]],"date-time":"2011-05-10T11:02:28Z","timestamp":1305025348000},"page":"538-550","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Adrenoceptor activity of muscarinic toxins identified from mamba venoms"],"prefix":"10.1111","volume":"164","author":[{"given":"K","family":"N\u00e4reoja","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JP","family":"Kukkonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Rondinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DM","family":"Toivola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Meriluoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"N\u00e4sman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(88)90025-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706048"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2006.09.023"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(99)00064-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(02)00278-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2006.09.022"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0031-6997(24)01362-0","article-title":"International Union of Pharmacology. 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