Enteric neural pathways inhibitory to rabbit duodenal serotonin release

Previous studies have shown that adrenergic and cholinergic neural pathways mediate duodenal serotonin (5-HT) release from the mucosal surface after a luminal acid stimulus. To examine the overall neural contribution to 5-HT release, we studied the effects of tetrodoxin (TTX), a nerve-conduction blocker, added to mucosal and/or serosal surfaces of rabbit duodenal mucosa in a modified Ussing chamber at both neutral and acid (pH 5) luminal pH. A specific radioimmunoassay was used to measure 5-HT. TTX (2 x 10^-7 M) increased mucosal 5-HT release significantly at luminal pH 7.4 and 5 when it was added to both mucosal and serosal surfaces (2.7- and 1.9-fold at pH 7.4 and pH 5, respectively; p < 0.05 for each) or when it was added to the serosal surface only (3.4- and 1.8-fold; p < 0.02 and p < 0.01, respectively). TTX added only to the mucosal surface, however, reduced 5-HT release by 48.5% at pH 5 (p < 0.01) and had no effect at pH 7.4. Since adenosine triphosphate (ATP) and vasoactive intestinal polypeptide are the two proposed mediators of a nonadrenergic, noncholinergic inhibitory neural system, we studied the effects of each on mucosal 5-HT release. While vasoactive intestinal polypeptide had no significant effect at either pH, ATP (10^-7 M) reduced acid-stimulated 5-HT release by approximately 50% (p < 0.02). We conclude that a nonadrenergic, noncholinergic neural pathway that is inhibitory to mucosal 5-HT release resides primarily on the basal surface of mucosal cells. ATP is the most likely neurotransmitter involved in this response.