C-type natriuretic peptide receptor expression in pancreatic alpha cells.
Atrial natriuretic peptide (ANP), brain type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) comprise a family of natriuretic peptides that mediate their biological effects through three natriuretic peptide receptor subtypes, NPR-A (ANP, BNP), NPR-B (CNP) and NPR-C (ANP, BNP, CNP). Several reports have provided evidence for the expression of ANP and specific binding sites for ANP in the pancreas. The purpose of this study was to identify the ANP receptor subtype and to localize its expression to a specific cell type in the human pancreas. NPR-C immunoreactivity, but neither ANP nor NPR-A, was detected in human islets by immunofluorescent staining. No immunostaining was observed in the exocrine pancreas or ductal structures. Double-staining revealed that NPR-C was expressed mainly in the glucagon-containing alpha cells. NPR-C mRNA and protein were detected in isolated human islets by RT-PCR and Western blot analysis, respectively. NPR-C expression was also detected by immunofluorescent staining in glucagonoma but not in insulinoma. ANP, as well as BNP and CNP, stimulated glucagon secretion from perifused human islets (1,111 +/- 55% vs. basal [7.3 fmol/min]; P < 0.001). This response was mimicked by cANP(4-23), a selective agonist of NPR-C. In conclusion, the NPR-C receptor is expressed in normal and neoplastic human alpha cells. These findings suggest a role for natriuretic peptides in the regulation of glucagon secretion from human alpha cells.
Surgery and Research & Development Services, James A. Haley VA Hospital, Research Service (151), 13000 Bruce B. Downs Boulevard, Tampa, FL 33612-4745, USA.
Matthew D
MD
Burgess
Kim D
KD
Moore
Gay M
GM
Carter
Abdel A
AA
Alli
Christopher S
CS
Granda
Hirohito
H
Ichii
Camillo
C
Ricordi
William R
WR
Gower
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D005935:Glucagonoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis*; D055815:Young Adult
D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C