title: Enterochromaffin-like cells in rat stomach respond to short-term infusion of high doses of cholecystokinin but not to long-term, sustained, moderate hyperCCKemia caused by continuous cholecystokinin infusion or pancreaticobiliary diversion.
abstract: The histamine-producing enterochromaffin-like (ECL) cells in the oxyntic mucosa are controlled by gastrin. An acute gastrin challenge induces release and accelerated resynthesis of ECL cell histamine. Long-term stimulation with gastrin causes ECL cell hyperplasia. We set out to study whether the ECL cells respond not only to gastrin but also to cholecystokinin (CCK). A wide dose range of gastrin-14 sulfated and -17 non-sulfated and CCK-8 sulfated (CCK-8s) and non-sulfated (CCK-8) was infused intravenously to rats for 3 h. The activity of the histamine-forming enzyme was measured at termination of infusion. Gastrins and CCK-8s were equally effective in activating the enzyme, whereas sulfated CCK-8 was notably less potent than the other three peptides. Clearly, the receptor responsible for activation of the ECL cells distinguishes poorly between gastrin-17 and CCK-8s, which is in line with the characteristics of the CCK-B receptor. Moreover, neither the response to gastrin-17 nor that to CCK-8s was affected by concomitant infusion of devazepide (200 micrograms/kg/h), a selective CCK-A-receptor antagonist. One group of rats received CCK-8s continuously via a minipump. Another group of rats was subjected to pancreaticobiliary diversion (PBD), which increases the plasma CCK concentration 10- to 20-fold. The rats were killed 7 or 10 weeks later, respectively, and the stomachs were analyzed with regard to mucosal growth and ECL cell hyperplasia. HyperCCKemic rats had increased pancreatic weights but showed no signs of growth stimulation in the stomach and no ECL cell hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Dept. of Pharmacology, University of Lund, Sweden.
authors.forename: A G
authors.initials: AG
authors.lastname: Nylander
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: I
authors.initials: I
authors.lastname: Lilja
authors.forename: J
authors.initials: J
authors.lastname: Axelson
authors.forename: I
authors.initials: I
authors.lastname: Ihse
authors.forename: J F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: F
authors.initials: F
authors.lastname: Sundler
authors.forename: R
authors.initials: R
authors.lastname: Håkanson
mesh_terms: D000818:Animals; D015904:Biliopancreatic Diversion; D002766:Cholecystokinin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D005755:Gastrins / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000096:biosynthesis / Q000187:drug effects; D006965:Hyperplasia; D007262:Infusions, Intravenous; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000166:cytology* / Q000187:drug effects
chemical_list: D005755:Gastrins; D002766:Cholecystokinin; D006640:Histidine Decarboxylase