{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:33:14Z","timestamp":1776087194259,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,3,29]],"date-time":"2012-03-29T00:00:00Z","timestamp":1332979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006954","name":"Tufts Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006954","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Three forms of serpinin peptides, serpinin (Ala26Leu), pyroglutaminated (pGlu)\u2010serpinin (pGlu23Leu), and serpinin\u2010Arg\u2010Arg\u2010Gly (Ala29Gly), are derived from cleavage at pairs of basic residues in the highly conserved C terminus of chromogranin A (CgA). Serpinin induces PN\u20101 expression in neuroendocrine cells to up\u2010regulate granule biogenesis\n                    <jats:italic>via<\/jats:italic>\n                    a cAMP\u2010protein kinase A\u2010Sp1 pathway, while pGlu\u2010serpinin inhibits cell death. The aim of this study was to test the hypothesis that serpinin peptides are produced in the heart and act as novel \u03b2\u2010adrenergic\u2010like cardiac modulators. We detected serpinin peptides in the rat heart by HPLC and ELISA methods. The peptides included predominantly Ala29Gly and pGlu\u2010serpinin and a small amount of serpinin. Using the Langendorff perfused rat heart to evaluate the hemodynamic changes, we found that serpinin and pGlu\u2010serpinin exert dose\u2010dependent positive inotropic and lusitropic effects at 11\u2013165 nM, within the first 5 min after administration. The pGlu\u2010serpinin\u2010induced contractility is more potent than that of serpinin, starting from 1 nM. Using the isolated rat papillary muscle preparation to measure contractility in terms of tension development and muscle length, we further corroborated the pGlu\u2010serpinin\u2010induced positive inotropism. Ala29Gly was unable to affect myocardial performance. Both pGlu\u2010serpinin and serpinin act through a \u03b21\u2010adrenergic receptor\/adenylate cyclase\/cAMP\/PKA pathway, indicating that, contrary to the \u03b2\u2010blocking profile of the other CgA\u2010derived cardiosuppressive peptides, vasostatin\u20101 and catestatin, these two C\u2010terminal peptides act as \u03b2\u2010adrenergic\u2010like agonists. In cardiac tissue extracts, pGluserpinin increased intracellular cAMP levels and phosphorylation of phospholamban (PLN)Ser16, ERK1\/2, and GSK\u20103\u03b2. Serpinin and pGlu\u2010serpinin peptides emerge as novel \u03b2\u2010adrenergic inotropic and lusitropic modulators, suggesting that CgA and the other derived cardioactive peptides can play a key role in how the myocardium orchestrates its complex response to sympathochromaffin stimulation.\u2014Tota, B., Gentile, S., Pasqua, T., Bassino, E., Koshimizu, H., Cawley, N. X., Cerra, M. C., Loh, Y. P., Angelone, T. The novel chromogranin A\u2010derived serpinin and pyroglutaminated serpinin peptides are positive cardiac \u03b2\u2010adrenergic\u2010like inotropes.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 2888\u20132898 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-201111","type":"journal-article","created":{"date-parts":[[2012,3,30]],"date-time":"2012-03-30T01:04:19Z","timestamp":1333069459000},"page":"2888-2898","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["The novel chromogranin A\u2010derived serpinin and pyroglutaminated serpinin peptides are positive cardiac \u03b2\u2010adrenergic\u2010like inotropes"],"prefix":"10.1096","volume":"26","author":[{"given":"Bruno","family":"Tota","sequence":"first","affiliation":[{"name":"Department of Cell Biology University of Calabria  Arcavacata di Rende Italy"}]},{"given":"Stefano","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Cell Biology University of Calabria  Arcavacata di Rende Italy"}]},{"given":"Teresa","family":"Pasqua","sequence":"additional","affiliation":[{"name":"Department of Cell Biology University of Calabria  Arcavacata di Rende Italy"}]},{"given":"Eleonora","family":"Bassino","sequence":"additional","affiliation":[{"name":"Department of Animal and Human Biology University of Turin  Turin Italy"}]},{"given":"Hisatsugu","family":"Koshimizu","sequence":"additional","affiliation":[{"name":"Section of Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health  Bethesda Maryland USA"}]},{"given":"Niamh X.","family":"Cawley","sequence":"additional","affiliation":[{"name":"Section of Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health  Bethesda Maryland USA"}]},{"given":"Maria C.","family":"Cerra","sequence":"additional","affiliation":[{"name":"Department of Cell Biology University of Calabria  Arcavacata di Rende Italy"},{"name":"Department of Pharmaco\u2010Biology University of Calabria  Arcavacata di Rende Italy"}]},{"given":"Y. Peng","family":"Loh","sequence":"additional","affiliation":[{"name":"Section of Cellular Neurobiology, Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health  Bethesda Maryland USA"}]},{"given":"Tommaso","family":"Angelone","sequence":"additional","affiliation":[{"name":"Department of Cell Biology University of Calabria  Arcavacata di Rende Italy"}]}],"member":"311","published-online":{"date-parts":[[2012,3,29]]},"reference":[{"key":"e_1_2_31_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90222-N"},{"key":"e_1_2_31_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7254-0"},{"key":"e_1_2_31_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/324476a0"},{"key":"e_1_2_31_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-110239"},{"key":"e_1_2_31_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24354"},{"key":"e_1_2_31_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.109.924050"},{"key":"e_1_2_31_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/38.6.2139887"},{"key":"e_1_2_31_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm022"},{"key":"e_1_2_31_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-010-1059-4"},{"key":"e_1_2_31_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198409203111204"},{"key":"e_1_2_31_12_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1360067"},{"key":"e_1_2_31_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.2001.2977"},{"key":"e_1_2_31_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn513"},{"key":"e_1_2_31_15_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/eurjhf\/hfq055","article-title":"Prognostic value of chromogranin A in chronic heart failure: data from the GISSI\u2010Heart Failure trial","volume":"12","author":"R\u2298sj\u2298 H.","year":"2010","journal-title":"Eur. 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