WE-14, a chromogranin a-derived neuropeptide

The neuropeptide WE-14 is derived from the posttranslational processing of chromogranin A (CgA). While CgA is expressed in a preponderance of neuroendocrine cells, WE-14 is generated in a distinct subpopulation of CgA-immunopositive cells, most notably in the adrenal, pituitary, and parathyroid glands. Physiological and pharmacological studies have demonstrated that CgA is cleaved to generate WE-14 in the adrenal chromaffin cell population and in the enterochromaffin-like (ECL) cells of the oxyntic mucosa. Pathological analyses of neuroendocrine tumors have revealed a heterogeneous pattern of WE-14 immunostaining, with variable concentrations quantified and chromatographically resolved in tissue extracts. Phylogenetic surveys have demonstrated that WE-14 exhibits an ancient lineage, while ontogenetic examination has shown that it is generated at an early stage during fetal development. Putative WE-14 receptor binding sites have been identified in several tissues; however, the physiological role of WE-14 remains enigmatic.