{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:35:24Z","timestamp":1791362124805,"version":"4.3.1"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1993,2]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND<\/jats:title>\n            <jats:p>In chronic heart failure, the positive inotropic effects of beta-adrenergic receptor agonists are greatly reduced, in part as a result of two alterations of the cardiac beta-adrenergic receptors: loss of their function (receptor uncoupling) and reduction of their number (downregulation). In vitro studies have shown that a major mechanism leading to beta-adrenergic receptor uncoupling involves phosphorylation of the receptors by the specific beta-adrenergic receptor kinase (beta ARK).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS AND RESULTS<\/jats:title>\n            <jats:p>We have therefore investigated expression of beta ARK and beta-adrenergic receptors in samples from the left ventricles of patients with dilated cardiomyopathy or ischemic cardiomyopathy and from nonfailing control ventricles. Contractile responses to beta-receptor stimulation were decreased in the failing hearts compared with control hearts, whereas those to forskolin and calcium remained unchanged. The messenger RNA (mRNA) levels of beta ARK, beta 1- and beta 2-receptors, and of glyceraldehyde phosphate dehydrogenase and beta-actin as controls were measured by quantitative polymerase chain reactions. In addition, beta ARK enzyme activity assays were performed, and the levels of beta 1- and beta 2-receptors were determined by radioligand binding. beta ARK mRNA levels were increased almost threefold in both forms of heart failure, and beta ARK activity was enhanced. beta 1-Receptor mRNA levels and beta 1-receptor numbers were decreased by approximately 50% in both failing groups, whereas these levels were unaltered for beta 2-receptors. There were no differences between dilated and ischemic cardiomyopathy for any of these parameters.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS<\/jats:title>\n            <jats:p>In addition to other alterations found in failing hearts, the diminished response to beta-receptor agonists appears to involve the combined effects of enhanced expression of beta ARK and reduced expression of beta 1-receptors.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/01.cir.87.2.454","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:01:09Z","timestamp":1339459269000},"page":"454-463","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":651,"title":["Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart."],"prefix":"10.1161","volume":"87","author":[{"given":"M","family":"Ungerer","sequence":"first","affiliation":[{"name":"Laboratorium f\u00fcr Molekulare Biologie, Universit\u00e4t M\u00fcnchen, Max-Planck-Institut f\u00fcr Biochemie, Martinsried, FRG."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Molekulare Biologie, Universit\u00e4t M\u00fcnchen, Max-Planck-Institut f\u00fcr Biochemie, Martinsried, FRG."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J S","family":"Elce","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Molekulare Biologie, Universit\u00e4t M\u00fcnchen, Max-Planck-Institut f\u00fcr Biochemie, Martinsried, FRG."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Erdmann","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Molekulare Biologie, Universit\u00e4t M\u00fcnchen, Max-Planck-Institut f\u00fcr Biochemie, Martinsried, FRG."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J","family":"Lohse","sequence":"additional","affiliation":[{"name":"Laboratorium f\u00fcr Molekulare Biologie, Universit\u00e4t M\u00fcnchen, Max-Planck-Institut f\u00fcr Biochemie, Martinsried, FRG."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/pdf\/10.1161\/01.CIR.87.2.454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T15:46:35Z","timestamp":1715528795000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.87.2.454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,2]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1993,2]]}},"alternative-id":["10.1161\/01.CIR.87.2.454"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.87.2.454","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,2]]},"assertion":[{"value":"1993-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}