The regulation of histamine release from oxyntic mucosa is complex bec
ause of two potential sources of histamine: mast cells and enterochrom
affin-like (ECL) cells. A gastrin-responsive histamine pool was identi
fied in the rat oxyntic mucosa two decades ago, but these ECL cells fr
om the rat have not yet been isolated or characterized in vitro. In vi
vo studies in canine and human mucosa have been more difficult because
of the high content of histamine in mast cells. Using enzyme-disperse
d canine oxyntic mucosal cells, we have studied regulation of histamin
e release from a mast cell-depleted fraction prepared by sequential el
utriation and density gradient. Histamine-like immunoreactivity was de
monstrated, using peroxidase-anti-peroxidase immunohistochemistry. Aft
er short-term culture, histamine was released in response to gastrin,
cholecystokinin, carbachol, and forskolin. Somatostatin potently and e
ffectively inhibited the response to gastrin. The cultures used for th
ese studies also contained somatostatin cells, and, furthermore, the r
esponse to gastrin was enhanced by incubation with monoclonal antibodi
es to somatostatin. The latter findings suggested that somatostatin wa
s acting in these cultures by a paracrine route. This pattern contrast
s with that obtained in previous studies of canine oxyntic mucosal mas
t cells.