Localization of neuroendocrine regulatory peptide-1 and-2 in human tissues

Neuroendocrine regulatory peptides NERP-1 and NERP-2 are novel amidated peptides derived from VGF, a polypeptide secreted from neurons and endocrine cells through a regulated pathway. To explore the localization of NERPs in human tissues, we performed immunohistochemistry analysis on tissues obtained at autopsy or surgery. In the hypothalamus, cell bodies that stained strongly for NERPs were observed in the supraoptic and paraventricular nucleus where vasopressin was abundant. Immunoreactive (ir) NERPs were detected in the islets of the pancreas, where they colocalized extensively with insulin, partially with glucagon, and not at all with somatostatin. Ir-NERPs were also detected in the thyroid and gastric antrum, where they colocalized with calcitonin and gastrin, respectively. NERPs are colocalized with insulin in an insulinoma specimen. NERPs are abundant in the pancreas, and the tissue contents of ir-NERP-1 and -2 in the pancreas were 4.5+/-2.2 and 1.0+/-0.3 pmol/g wet tissue, respectively. NERPs were also detected in the thyroid and gastric antrum. Ir-NERPs of the human pancreas, thyroid and gastric antrum behaved identically to synthetic human NERP-1 or -2 on reverse phase-high performance liquid chromatography combined with radioimmunoassay. These results suggested that NERPs might function as local modulators in the human neuroendocrine system.