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

Am J Physiol. 1995 Feb;268(2 Pt 1):G339-45. doi: 10.1152/ajpgi.1995.268.2.G339.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amylases / antagonists & inhibitors*
  • Amylases / metabolism
  • Animals
  • Female
  • Ganglia / physiology*
  • In Vitro Techniques
  • Neurons / metabolism
  • Pancreas / cytology
  • Pancreas / innervation*
  • Pancreas / metabolism*
  • Presynaptic Terminals / drug effects*
  • Presynaptic Terminals / physiology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Serotonin / pharmacology*
  • Veratridine / pharmacology

Substances

  • Proto-Oncogene Proteins c-fos
  • Serotonin
  • Veratridine
  • Amylases