In order to identify proguanylin-secreting cells, we have raised an antiser
um against the synthetic fragment of human proguanylin (1-15) and have exam
ined the proguanylin-positive cells in the human and rat gastrointestinal t
ract by immunohistochemical methods. Numerous proguanylin (1-15)immunoreact
ive cells were found in the gastrointestinal tract. They were either pyrami
dal or spindle shaped in the stomach. Spindle-shaped cells, frequently poss
essing long slender processes, were located at the base of the pyloric epit
helium and did not extend to the lumen. In the duodenum and jejunum, these
cells were mostly pyramidal in shape and often had a slender process toward
s the lumen. The immunostaining was completely blocked by the human proguan
ylin (1-15) fragment. Paneth and goblet cells were negative against this an
tiserum. The number of serotonin-positive cells was much larger than that o
f proguanylin-positive cells in all the segments tested. The number of prog
uanylin-positive cells decreased from the jejunum to the ileum and very few
cells were observed in the colon. In contrast to serotonin-positive cells,
most somatostatin-positive cells were also positive for proguanylin. Thus,
proguanylin (1-15) or its related protein appears to coexist with somatost
atin in intestinal endocrine D cells which may be a source of circulating p
roguanylin. Proguanylin, like somatostatin, may also regulate intestinal fu
nction as a local regulator.