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 μg/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. These findings are also in line with the view that the receptor responsible for growth of the pancreas is of the CCK-A type, while the one responsible for growth of the ECL cells and of the oxyntic mucosa is of the CCK-B type. Nonetheless, the complete lack of trophic effect of long-term hyperCCKemia on the stomach was surprising. The most likely explanation is that even in the hyperCCKemic rat the plasma CCK concentrations were too low to activate the CCK-B-type receptor, being 5- to 10-fold lower than the normal concentrations of gastrin in the circulation.

Key Words:

• Cholecystokinin
• enterochromaffin-like cells
• gastrin
• hyperCCKemia
• pancreaticobiliary diversion
• rat