Abstract
Previous studies have shown that atrial natriuretic peptide (ANP) regulates exocrine pancreatic function in health and disease. As extracardiac sources of ANP have been identified and ANP-like immunoreactivity has been reported in the exocrine pancreas, in the present work we sought to establish whether ANP was produced in the rat exocrine pancreas and if conditions like fasting/feeding or acute pancreatitis were reflected on ANP expression. By using RT-PCR, immunoblotting, and immunofluorescence microscopy assays, it was found that both mRNA and protein ANP were present in the acinar cells of the exocrine pancreas. The amount of ANP in the pancreas was lower in than the atrium but similar to other tissues like the kidney and liver. Immunogold labeling electron microscopy studies revealed that ANP was localized in zymogen granules and the endoplasmic reticulum suggesting local synthesis and package into granules. ANP protein expression was significantly increased not only in fasting but also in acute pancreatitis, the latter probably related to impaired secretion. Natriuretic peptide receptor type C which mediates ANP biological effects in the exocrine pancreas was also present in acinar cells and its expression did not change with either fasting or acute pancreatitis. Present findings show that the exocrine pancreas is a relatively important extracardiac source of ANP and further support previous studies strongly suggesting the active role of the peptide in pancreatic physiology and pathophysiology.
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Acknowledgments
The authors thank Mrs. Margarita Lopez from the Instituto de Biologia Celular y Neurociencia (IBCN-CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires for excellent technical assistance with immunogold labeling studies.
Funding
This work was supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) (PICT2012-2755 and PICT2015-2030) and Universidad de Buenos Aires (UBACYT 20020130100811BA).
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Najenson, A.C., Bianchi, M., Courreges, A.P. et al. The exocrine pancreas is an extracardiac source of atrial natriuretic peptide. Pflugers Arch - Eur J Physiol 471, 915–924 (2019). https://doi.org/10.1007/s00424-018-02247-y
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DOI: https://doi.org/10.1007/s00424-018-02247-y