Vagal, Cholinergic Regulation of Pancreatic Polypeptide Secretion

J Clin Invest. 1978 Mar;61(3):781-9. doi: 10.1172/JCI108992.

Abstract

THE EFFECT OF EFFERENT, PARASYMPATHETIC STIMULATION UPON PANCREATIC POLYPEPTIDE (PP) SECRETION WAS STUDIED IN THREE WAYS: (a) Plasma PP concentrations increased in response to insulin-induced hypoglycemia in both normal subjects, from 11 pM (9.5-12.5) to 136 pM (118-147), n = 8 (median and interquartile range) and in duodenal ulcer patients, from 33 pM (21-52) to 213 pM (157-233), n = 7. The PP response to hypoglycemia was diminished by atropine in normal subjects (P < 0.005) and completely abolished by vagotomy in the duodenal ulcer patients. (b) Electrical stimulation, 8 Hz, of the vagal nerves in anesthetized pigs induced an increase in portal PP concentrations within 30 s from 32 pM (28-39) to 285 pM (248-294), n = 12. Minimal stimulatory frequency was 0.5 Hz and maximal stimulatory frequency 8-12 Hz. Atropine inhibited the PP response to electrical stimulation. Median inhibition with 0.5 mg of atropine/kg body wt was 74%, range 31-90%, n = 6. The response was eliminated by hexamethonium. Adrenergic alpha and beta blockade did not influence the release of PP in response to vagal stimulation. (c) Acetylcholine stimulated, in a dose-dependent manner, the secretion of PP from the isolated perfused porcine pancreas, half-maximal effective dose being 0.19 muM; maximal PP output in response to 5 min stimulation was 228 pmol, range 140-342 pmol, n = 5. Atropine completely abolished this response.The results of the present study together with the previously demonstrated poor PP response to food in vagotomized patients, indicate that vagal, cholinergic stimulation is a major regulator of PP secretion.

MeSH terms

  • Acetylcholine / pharmacology
  • Adult
  • Animals
  • Antibody Specificity
  • Atropine / pharmacology
  • Duodenal Ulcer / metabolism
  • Electric Stimulation
  • Female
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / metabolism
  • In Vitro Techniques
  • Insulin / pharmacology
  • Male
  • Middle Aged
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Pancreatic Hormones / blood
  • Pancreatic Hormones / metabolism*
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / physiology*
  • Peptides / blood
  • Peptides / metabolism*
  • Perfusion
  • Radioimmunoassay
  • Swine
  • Vagotomy
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology*

Substances

  • Insulin
  • Pancreatic Hormones
  • Peptides
  • Atropine
  • Acetylcholine