{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T07:08:37Z","timestamp":1777100917192,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":790,"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":[[2006,12]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>This study was carried out to elucidate which \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor subtypes mediated the inhibition of noradrenaline and adrenaline release from the adrenal medulla of mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Isolated adrenal medullae from wild\u2010type and \u03b1<jats:sub>2A<\/jats:sub>, \u03b1<jats:sub>2B<\/jats:sub> and \u03b1<jats:sub>2C<\/jats:sub>\u2010adrenoceptor knockout (KO) mice were placed in superfusion chambers. Catecholamine overflow was evoked by 1,1\u2010dimethyl\u20104\u2010phenylpiperazinium (500 \u03bcM) in absence or in presence of the \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonist medetomidine. The effect of medetomidine was tested in presence of the \u03b1\u2010adrenoceptor antagonists rauwolscine, WB 4101, spiroxatrine, phentolamine and prazosin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>In wild\u2010type mice, medetomidine reduced noradrenaline and adrenaline overflow in a concentration\u2010dependent manner (EC<jats:sub>50<\/jats:sub> in nM: 1.54 and 1.92; E<jats:sub>max<\/jats:sub> in % of inhibition: 91 and 94, for noradrenaline and adrenaline, respectively). The p<jats:italic>K<\/jats:italic>\n<jats:sub>D<\/jats:sub> values of the antagonists for noradrenaline overflow did not correlate with pK<jats:sub>D<\/jats:sub> values at \u03b1<jats:sub>2A<\/jats:sub>, \u03b1<jats:sub>2B<\/jats:sub>, or \u03b1<jats:sub>2C<\/jats:sub> binding sites. The p<jats:italic>K<\/jats:italic>\n<jats:sub>D<\/jats:sub> values of the antagonists for adrenaline overflow correlated positively with pK<jats:sub>D<\/jats:sub> values at \u03b1<jats:sub>2C<\/jats:sub> binding sites (opossum kidney cells). The effect of medetomidine (100 nM) on noradrenaline overflow was significantly reduced in all three \u03b1<jats:sub>2<\/jats:sub>KO mice (57, 54, 44 % inhibition, for \u03b1<jats:sub>2A<\/jats:sub>, \u03b1<jats:sub>2B<\/jats:sub>, and \u03b1<jats:sub>2C<\/jats:sub>, respectively), whereas the effect of medetomidine on adrenaline overflow was greatly reduced in \u03b1<jats:sub>2C<\/jats:sub>KO mice (14 % inhibition).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>In the adrenal medulla of mice, all three \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor subtypes (\u03b1<jats:sub>2A<\/jats:sub>, \u03b1<jats:sub>2B<\/jats:sub>, and \u03b1<jats:sub>2C<\/jats:sub>) play an equal role in the inhibition of noradrenaline overflow, whereas the \u03b1<jats:sub>2C<\/jats:sub>\u2010adrenoceptor is the predominant \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor subtype involved in the inhibitory mechanism controlling adrenaline overflow.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2006) <jats:bold>149<\/jats:bold>, 1049\u20131058. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706950\">10.1038\/sj.bjp.0706950<\/jats:ext-link> Published online 30 October 2006<\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0706950","type":"journal-article","created":{"date-parts":[[2006,10,30]],"date-time":"2006-10-30T15:31:30Z","timestamp":1162222290000},"page":"1049-1058","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["<i>\u03b1<\/i><sub>2<\/sub>\u2010Adrenoceptor subtypes involved in the regulation of catecholamine release from the adrenal medulla of mice"],"prefix":"10.1111","volume":"149","author":[{"given":"E","family":"Moura","sequence":"first","affiliation":[]},{"given":"J","family":"Afonso","sequence":"additional","affiliation":[]},{"given":"L","family":"Hein","sequence":"additional","affiliation":[]},{"given":"M A","family":"Vieira\u2010Coelho","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.56.1.154"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90823-8"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201x.1999.00580.x"},{"key":"e_1_2_8_5_1","first-page":"323","article-title":"Characterization of the alpha\u20102C adrenergic receptor subtype in the opossum kidney and in the OK cell line","volume":"259","author":"Blaxall HS","year":"1991","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.1996.0130"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.26.14742"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0035"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000036600.39600.66"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67031217.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1242\/dev.126.13.2935","article-title":"Analysis of mice carrying targeted mutations of the glucocorticoid receptor gene argues against an essential role of glucocorticoid signalling for generating adrenal chromaffin cells","volume":"126","author":"Finotto S","year":"1999","journal-title":"Development"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02510.x"},{"key":"e_1_2_8_14_1","first-page":"228","volume-title":"Catecholamines. 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