Secretoneurin is a functional neuropeptide derived from secretogranin
II (chromogranin C). This proprotein is processed to varying degrees i
n neuroendocrine tissues. In the present study we established by gel f
iltration high performance liquid chromatography that in human intesti
nal wall and mucosa an antiserum against secretoneurin detects as the
major immunoreactive moiety the free peptide secretoneurin. In the muc
osa some larger immunoreactive peptides were also present, however, a
significant amount of the intact proprotein secretogranin II could not
be detected. By immunohistochemistry we studied the distribution of s
ecretoneurin within the gut. Antibodies to protein gene product 9.5 an
d chromogranin A were used to identify all neurons and endocrine cells
, respectively, whilst those to the peptides substance P, CGRP and som
atostatin were used for the further characterization of individual sec
retoneurin-positive structures. Secretoneurin immunoreactivity was fou
nd in nerve fibres in all layers of the gut wall. In both myenteric an
d submucous plexuses, nerve fibres and the majority of ganglion cells
were secretoneurin-immunoreactive. In the mucosa, some secretoneurin-p
ositive nerve processes ran parallel to the basal membrane of epitheli
al cells, occasionally invading the epithelial layer. Secretoneurin im
munoreactivity was found in endocrine cells, mostly D cells, in the fo
llowing regions in descending order of density: stomach/duodenum; rect
um; colon; ileum. Thus, secretoneurin is a new major peptide within th
e human enteric neuroendocrine system. Its presence in abundant myente
ric ganglion cells may imply a role in the modulation of gastrointesti
nal motility. The chemotactic properties of secretoneurin and its poss
ible localization in sensory fibres suggest that this peptide may be i
nvolved in the genesis of intestinal inflammation.