{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T16:33:12Z","timestamp":1775061192008,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3348,"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":[[1999,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>We identified putative \u03b2<jats:sub>4<\/jats:sub>\u2010adrenoceptors by radioligand binding, measured increases in ventricular contractile force by (\u2212)\u2010CGP 12177 and (\u00b1)\u2010cyanopindolol and demonstrated increased Ca<jats:sup>2+<\/jats:sup> transients by (\u2212)\u2010CGP 12177 in rat cardiomyocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>(\u2212)\u2010[<jats:sup>3<\/jats:sup>H]\u2010CGP 12177 labelled 13\u201322\u2003fmol\u2003mg<jats:sup>\u22121<\/jats:sup> protein ventricular \u03b2<jats:sub>1<\/jats:sub>, \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptors (pK<jats:sub>D<\/jats:sub> \u223c9.0) and 50\u201390\u2003fmol\u2003mg<jats:sup>\u22121<\/jats:sup> protein putative \u03b2<jats:sub>4<\/jats:sub>\u2010adrenoceptors (pK<jats:sub>D<\/jats:sub> \u223c7.3). The affinity values (pK<jats:sub>i<\/jats:sub>) for (\u03b2<jats:sub>1<\/jats:sub>,\u03b2<jats:sub>2<\/jats:sub>\u2010) and putative \u03b2<jats:sub>4<\/jats:sub>\u2010adrenoceptors, estimated from binding inhibition, were (\u2212)\u2010propranolol 8.4, 5.7; (\u2212)\u2010bupranolol 9.7, 5.8; (\u00b1)\u2010cyanopindolol 10.0,7.4.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In left ventricular papillary muscle, in the presence of 30\u2003\u03bc<jats:sc>M<\/jats:sc> 3\u2010isobutyl\u20101\u2010methylxanthine, (\u2212)\u2010CGP 12177 and (\u00b1)\u2010cyanopindolol caused positive inotropic effects, (pEC<jats:sub>50<\/jats:sub>, (\u2212)\u2010CGP 12177, 7.6; (\u00b1)\u2010cyanopindolol, 7.0) which were antagonized by (\u2212)\u2010bupranolol (pK<jats:sub>B<\/jats:sub> 6.7\u20137.0) and (\u2212)\u2010CGP 20712A (pK<jats:sub>B<\/jats:sub> 6.3\u20136.6). The cardiostimulant effects of (\u2212)\u2010CGP 12177 in papillary muscle, left and right atrium were antagonized by (\u00b1)\u2010cyanopindolol (pK<jats:sub>P<\/jats:sub> 7.0\u20137.4).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>(\u2212)\u2010CGP 12177 (1\u2003\u03bc<jats:sc>M<\/jats:sc>) in the presence of 200\u2003n<jats:sc>M<\/jats:sc> (\u2212)\u2010propranolol increased Ca<jats:sup>2+<\/jats:sup> transient amplitude by 56% in atrial myocytes, but only caused a marginal increase in ventricular myocytes. In the presence of 1\u2003\u03bc<jats:sc>M<\/jats:sc> 3\u2010isobutyl\u20101\u2010methylxanthine and 200\u2003n<jats:sc>M<\/jats:sc> (\u2212)\u2010propranolol, 1\u2003\u03bc<jats:sc>M<\/jats:sc> (\u2212)\u2010CGP 12177 caused a 73% increase in Ca<jats:sup>2+<\/jats:sup> transient amplitude in ventricular myocytes. (\u2212)\u2010CGP 12177 elicited arrhythmic transients in some atrial and ventricular myocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Probably by preventing cyclic AMP hydrolysis, 3\u2010isobutyl\u20101\u2010methylxanthine facilitates the inotropic function of ventricular putative \u03b2<jats:sub>4<\/jats:sub>\u2010adrenoceptors, suggesting coupling to G<jats:sub>s<\/jats:sub> protein\u2010adenylyl cyclase. The receptor\u2010mediated increases in contractile force are related to increases of Ca<jats:sup>2+<\/jats:sup> in atrial and ventricular myocytes. The agreement of binding affinities of agonists with cardiostimulant potencies is consistent with mediation through putative \u03b2<jats:sub>4<\/jats:sub>\u2010adrenoceptors labelled with (\u2212)\u2010[<jats:sup>3<\/jats:sup>H]\u2010CGP 12177.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 1445\u20131460; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702936\">10.1038\/sj.bjp.0702936<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702936","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:28:56Z","timestamp":1106944136000},"page":"1445-1460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Putative \u03b2<sub>4<\/sub>\u2010adrenoceptors in rat ventricle mediate increases in contractile force and cell Ca<sup>2+<\/sup>: comparison with atrial receptors and relationship to (\u2212)\u2010[<sup>3<\/sup>H]\u2010CGP 12177 binding"],"prefix":"10.1111","volume":"128","author":[{"given":"Doreen","family":"Sarsero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Molenaar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto J","family":"Kaumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas S","family":"Freestone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1965.20.4.755"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050728"},{"key":"e_1_2_7_4_1","first-page":"I","article-title":"Functional \u03b23\u2010adrenergic receptors in the canine myocardium","volume":"98","author":"CHENG H.\u2010J.","year":"1998","journal-title":"Circulation (abstract)"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002109900075"},{"key":"e_1_2_7_7_1","first-page":"74","article-title":"Activation of an atypical \u03b2\u2010adrenoceptor increases calcium and can elicit arrhythmias in rat atrial cardiomyocytes","volume":"39","author":"FREESTONE N.","year":"1997","journal-title":"The Pharmacologist"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00408662"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2191"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118823"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00498852"},{"key":"e_1_2_7_12_1","first-page":"I","article-title":"Lack of evidence for \u03b23\u2010adrenoceptor modulation of contractile function in human ventricular myocytes","volume":"96","author":"HARDING S.","year":"1997","journal-title":"Circulation"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(88)80121-4"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00500096"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(89)90065-5"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15159.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(96)01033-4"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.1.65"},{"key":"e_1_2_7_19_1","first-page":"74","article-title":"Atypical \u03b2\u2010adrenoceptor activation by (\u2212)\u2010CGP 12177 increases cytosolic calcium in rat ventricular myocytes","volume":"39","author":"KAUMANN A.J.","year":"1997","journal-title":"The Pharmacologist"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701053"},{"key":"e_1_2_7_21_1","first-page":"102P","article-title":"The atypical cardiostimulant \u03b2\u2010adrenoceptor is distinct from \u03b23\u2010adrenoceptors and coupled to a cyclic AMP\u2010dependent pathway in human and rat myocardium","volume":"120","author":"KAUMANN A.J.","year":"1997","journal-title":"Br. 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