title: Presynaptic inhibition by serotonin of nerve-mediated secretion of pancreatic amylase.
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.
authors.affiliation: Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: A L
authors.initials: AL
authors.lastname: Kirchgessner
authors.forename: M D
authors.initials: MD
authors.lastname: Gershon
mesh_terms: D000681:Amylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D005260:Female; D005724:Ganglia / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000294:innervation* / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin; D014701:Veratridine; D000681:Amylases