Presynaptic inhibition by serotonin of nerve-mediated secretion of pancreatic amylase.

Enteric cholinergic and serotonergic neurons innervate pancreatic ganglia. Enteropancreatic cholinergic neurons are secretomotor, bu the function of the serotonergic cells is unknown and was investigated. Postganglionic cholinergic nerve-mediated amylase secretion was evoked by veratridine in isolated pancreatic lobules. This concentration-dependent response was inhibited by tetrodotoxin (1.0 microM), atropine (5.0 microM), 5-hydroxytryptamine (5-HT; 5.0 microM), 5-hydroxyindalpine (5-OHIP; 10.0 microM; a 5-HT1P agonist), and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 microM), but not by hexamethonium (100.0 microM), 2-methyl-5-HT (10 microM), or 5-carboxyamidotryptamine (10 microM). The effects of 5-HT and 5-OHIP were blocked by the 5-HT1P antagonist N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP; 100.0 microM). Carbachol (5.0 microM)-evoked secretion was not affected by 5-HT or 5-OHIP. Veratridine induced c-fos expression in pancreatic neurons and acinar cells. This expression was inhibited by tetrodotoxin, 5-HT, and 5-OHIP. These observations suggest that the serotonergic enteropancreatic innervation inhibits pancreatic secretion via presynaptic receptors on cholinergic nerves. Although the data are consistent with the hypothesis that the inhibitory receptor is a 5-HT1P site, positive identification awaits further study.