title: Cardiomyocyte expression and cell-specific processing of procholecystokinin.
abstract: Heart muscle cells produce peptide hormones such as natriuretic peptides. Developing hearts also express the gene for the classic intestinal hormone cholecystokinin (CCK) in amounts similar to those in the intestine and brain. However, cardiac expression of peptides other than natriuretic peptides has only been suggested using transcriptional measures or methods, with the post-translational phase of gene expression unaddressed. In this study, we examined the cardiac expression of the CCK gene in adult mammals and its expression at the protein level. Using quantitative PCR, a library of sequence-specific pro-CCK assays, peptide purification, and mass spectrometry, we demonstrate that the mammalian heart expresses pro-CCK in amounts comparable to natriuretic prohormones and processes it to a unique, triple-sulfated, and N-terminally truncated product distinct from intestinal and cerebral CCK peptides. Isoprenaline rapidly stimulated cardiac CCK gene expression in vitro and in vivo, which suggests that the cardiac-specific truncated pro-CCK may have pathophysiological relevance as a new marker of heart failure. The suggestion is confirmed by measurement of plasma from heart failure patients.
authors: From the Departments of Clinical Biochemistry and Cardiology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark the Department of Endocrinology, Herlev Hospital, University of Copenhagen, 2730 Herlev, and jpg@dadlnet.dk.
authors: Jens P
authors: JP
authors: Goetze
authors: From the Departments of Clinical Biochemistry and Cardiology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, the Department of Endocrinology, Herlev Hospital, University of Copenhagen, 2730 Herlev, and.
authors: Anders H
authors: AH
authors: Johnsen
authors: From the Departments of Clinical Biochemistry and Cardiology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, the Department of Endocrinology, Herlev Hospital, University of Copenhagen, 2730 Herlev, and.
authors: Caroline
authors: C
authors: Kistorp
authors: From the Departments of Clinical Biochemistry and Cardiology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, the Department of Endocrinology, Herlev Hospital, University of Copenhagen, 2730 Herlev, and.
authors: Finn
authors: F
authors: Gustafsson
authors: From the Departments of Clinical Biochemistry and Cardiology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, the Department of Endocrinology, Herlev Hospital, University of Copenhagen, 2730 Herlev, and.
authors: Camilla B
authors: CB
authors: Johnbeck
authors: From the Departments of Clinical Biochemistry and Cardiology, Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, the Department of Endocrinology, Herlev Hospital, University of Copenhagen, 2730 Herlev, and jens.f.rehfeld@regionh.dk.
authors: Jens F
authors: JF
authors: Rehfeld
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D002460:Cell Line; D002766:Cholecystokinin / Q000032:analysis* / Q000097:blood / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011379:Prognosis; D011498:Protein Precursors / Q000032:analysis* / Q000097:blood / Q000235:genetics*; D051381:Rats; D013552:Swine
chemical_list: D002316:Cardiotonic Agents; D011498:Protein Precursors; C060249:procholecystokinin; D002766:Cholecystokinin; D007545:Isoproterenol
keywords: ANP; BNP; Cholecystokinin; Gene Expression; Gut Hormone; Heart; Heart Failure; Hormone; Natriuretic Peptide; Peptide Identification
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