Salmon cardiac peptide (sCP): a new model for natriuretic peptide biology
1University of Oulu, Faculty of Medicine, Department of Physiology
2University of Oulu, Biocenter Oulu
|Online Access:||PDF Full Text (PDF, 1.2 MB)|
|Persistent link:|| http://urn.fi/urn:isbn:9514264932
|Publish Date:|| 2001-09-18
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in the Auditorium of the Department of Physiology, on October 5th, 2001, at 12 noon.
Professor Mikko Nikinmaa
Professor Kerstin Olsson
Natriuretic peptide hormones secreted from the heart are important in maintaining the volume and electrolyte balance and in regulation of blood pressure. The secretion of natriuretic peptides is stimulated by myocyte stretch and paracrine factors. However, the intracellular actions of these stimuli and the cellular and molecular mechanisms involved in the processing and secretion of natriuretic peptides are still largely unknown. In this study, a new model for studies of the natriuretic peptide system was developed using a novel natriuretic peptide from salmon.
Salmon (Salmo salar) maintains its water and salt homeostasis despite the volume gain in fresh water and electrolyte gain in sea water. Thus, salmon is an ideal model to study the mechanisms regulating the extracellular volume and salt balance, like natriuretic peptides. Furthermore, comparative studies revealing the common characteristics in phylogenetically distinct species suggest the importance of these factors in the regulation of the natriuretic peptide system.
A novel natriuretic peptide, salmon cardiac peptide (sCP), was cloned from salmon heart. Distribution of sCP was studied in a variety of vertebrates and its physiological effects were examined in in vitro and in vivo experiments in salmon and rats. The storage and release of sCP was studied using a salmon ventricle perfusion system and by analysing the molecular forms of stored and secreted forms. Factors modulating the secretion and circulating concentration of sCP, and cardiac peptide and sCP mRNA level in salmon were examined as well.
The biosynthesis of sCP is strictly restricted to the heart. sCP is stored in myocytes in the prohormone form, while the secreted form is a 29-amino acid peptide in salmon. Mechanical load on isolated salmon ventricle and volume overload in intact salmon induced a rapid release of sCP. Exposure to hyperosmotic environment decreased the plasma sCP level. sCP increased diuresis and natriuresis, as well as relaxed preconstricted arteries from salmon and rats. Thus the storage, processing and release of sCP resembles those of mammalian ANP. The circulating level of sCP in salmon was markedly upregulated at increased temperatures. Upregulation resulted from decreased elimination rather than increased secretion of sCP, providing the first direct evidence that elimination is used for the regulation of the natriuretic peptide system. In conclusion, sCP is a promising model for studying the general factors regulating the cardiac natriuretic peptides.
Acta Universitatis Ouluensis. D, Medica
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