Vagal, cholinergic regulation of pancreatic polypeptide secretion.
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.
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000818:Animals; D000918:Antibody Specificity; D001285:Atropine / Q000494:pharmacology; D004381:Duodenal Ulcer / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010187:Pancreatic Hormones / Q000097:blood / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D010477:Perfusion; D011863:Radioimmunoassay; D013552:Swine; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D007328:Insulin; D010187:Pancreatic Hormones; D010455:Peptides; D001285:Atropine; D000109:Acetylcholine