Expression of Natriuretic Peptide Receptor C in Pancreatic Alpha Cells

Specific binding sites for atrial natriuretic peptide have been located in the islet cells of the pancreas. The identification of the receptor subtype and the localization of the receptor to a specific islet cell type in the human pancreas have not been reported. The aim of this study was to localize natriuretic peptide receptor subtypes A (NPR‐A) and C (NPR‐C) expression in normal and neoplastic human islets. Cell type specific localization of NPR‐A and NPR‐C proteins was examined by immunohistochemistry of normal and neoplastic human pancreas. Presence of receptor transcripts and proteins were determined by RT‐PCR and immunoblot analysis. Immunoreactive NPR‐C, but not NPR‐A, was detected in human islet cells. No immunostaining was observed in the exocrine pancreas or ductal structures. Double‐staining revealed that the NPR‐C receptors were expressed mainly in virtually all of the glucagon‐containing alpha cells. Immunoblot results demonstrated a ~60 kDa protein corresponding to NPR‐C in protein extracts of isolated human islets. NPR‐C expression in human islets was confirmed by RT‐PCR. NPR‐C expression was also detected by immunohistochemistry in glucagonoma but not in insulinoma or gastrinoma. The NPR‐C receptor is expressed in normal and neoplastic human alpha cells. This finding suggests a role for natriuretic peptides in the regulation of glucagon secretion from human alpha cells. This work was supported by grants from the Veterans Administration and NIH.