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Only in the additional presence of 0.1\u00a0\u00b5M rolipram, an inhibitor of the activity of phosphodiesterase IV, levosimendan increased force of contraction in LA and increased the phosphorylation state of phospholamban at amino acid serine 16. Levosimendan alone increased the beating rate in isolated spontaneously beating right atrial preparations from mice and this effect was potentiated by rolipram. The positive inotropic and the positive chronotropic effects of levosimendan in mouse atrial preparations were attenuated by 10\u00a0\u00b5M propranolol. Finally, we studied the contractile effects of levosimendan in isolated electrically stimulated (1\u00a0Hz) right atrial preparations from the human atrium (HAP), obtained during cardiac surgery. We detected concentration-dependent positive inotropic effects of levosimendan alone that reached plateau at 1\u00a0\u00b5M levosimendan in HAP (<jats:italic>n<\/jats:italic>\u2009=\u200911). Levosimendan shortened time of tension relaxation in HAP. Cilostamide (1\u00a0\u00b5M), an inhibitor of phosphodiesterase III, or propranolol (10\u00a0\u00b5M) blocked the positive inotropic effect of levosimendan in HAP. Levosimendan (1\u00a0\u00b5M) alone increased in HAP the phosphorylation state of phospholamban. In conclusion, we present evidence that levosimendan acts via phosphodiesterase III inhibition in the human atrium leading to phospholamban phosphorylation and thus explaining the positive inotropic effects of levosimendan in HAP.<\/jats:p>","DOI":"10.1007\/s00210-022-02348-7","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T08:10:40Z","timestamp":1669709440000},"page":"669-682","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Levosimendan increases the phosphorylation state of phospholamban in the isolated human atrium"],"prefix":"10.1007","volume":"396","author":[{"given":"Lina Maria Rayo","family":"Abella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Gergs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"2348_CR1","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1161\/CIRCRESAHA.109.197947","volume":"105","author":"A Abi-Gerges","year":"2009","unstructured":"Abi-Gerges A, Richter W, Lefebvre F, Mateo P, Varin A, Heymes C, Samuel J-L, Lugnier C, Conti M, Fischmeister R, Vandecasteele G (2009) Decreased expression and activity of cAMP phosphodiesterases in cardiac hypertrophy and its impact on \u03b2-adrenergic cAMP signals. 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