Stimulation of gastrin secretion in vitro by intraluminal chemicals: regulation by intramural cholinergic and noncholinergic neurons.

The regulation of gastrin and somatostatin secretion by intraluminal chemicals was examined in an isolated vascularly perfused rat stomach, a preparation that maintains the integrity of intramural neural pathways and the polarity of stimulation. Intraluminal perfusion with alkaline solutions (0.1 M NaHCO3) increased gastrin secretion, whereas perfusion with acid solutions (pH 3.5-3.0) inhibited gastrin secretion. Perfusion with 0.5% or 5% peptone solutions stimulated gastrin secretion and inhibited somatostatin secretion. Both these responses were abolished by addition of the axonal blocker, tetrodotoxin (10(-6) M), to the vascular perfusate, from which it was concluded that gastrin and somatostatin responses induced by peptone were mediated by intramural neurons. These neurons were both cholinergic and noncholinergic, because addition of an optimal dose of atropine (10(-7) M) to the vascular perfusate inhibited only partially the gastrin response and converted the somatostatin response from decrease below basal levels--a typical cholinergic effect--to significant increase above basal levels. As shown previously, atropine had an identical effect on gastrin and somatostatin responses to transmural electrical stimulation of the antral region. The results are in accord with a model for the regulation of gastrin secretion by intramural cholinergic and noncholinergic neurons. A direct effect of intraluminal chemicals on gastrin and somatostatin cells was not detected in this study, but is not precluded.