Role of pylorus in mediating cholecystokinin-stimulated satiety in the Zucker rat.

Obese Zucker rats are less responsive than their lean littermates to the effects of cholecystokinin-octapeptide on satiety and pancreatic growth and exocrine function. We hypothesized that the hyperphagia observed in obese Zucker rats may be caused by a decreased pyloric contractile response to cholecystokinin, resulting in an increased rate of gastric emptying, decreased postprandial gastric distention, and thus decreased satiety. Pyloric muscle strips from six obese Zucker rats and six lean littermates were mounted in separate tissue baths and isometric contraction was measured in response to acetylcholine and cholecystokinin-octapeptide. The dose-response curves for acetylcholine- and cholecystokinin-octapeptide-stimulated pyloric muscle contraction were similar for both the obese and the lean rats. (For cholecystokinin, D50 obese = 4.0 +/- 0.6 nM, D50 lean = 3.4 +/- 0.2 nM; P = 0.16). We conclude that the decreased satiety response to cholecystokinin-octapeptide observed in obese Zucker rats is not secondary to a decreased pyloric responsiveness to cholecystokinin.

The effect of somatostatin and 16,16-dimethyl-prostaglandin E2 on bombesin-stimulated canine gastric acid, plasma gastrin and pancreatic polypeptide secretion.

We studied the effect of the intravenous infusion of 16,16-dimethylprostaglandin E2 methyl ester (di-M-PGE2) and somatostatin on bombesin-stimulated gastric acid secretion, plasma gastrin and plasma pancreatic polypeptide in four chronic gastric fistula dogs. Bombesin-stimulated gastric acid secretion was significantly inhibited by somatostatin and virtually abolished by di-M-PGE2. Both agents caused significant, but indistinguishable inhibition of gastrin release (P less than 0.05). Bombesin-stimulated pancreatic polypeptide release was also significantly inhibited by both somatostatin and di-M-PGE2; the inhibitory effect of somatostatin was significantly greater than that of di-M-PGE2 (P less than 0.05). This study provides further evidence in support of the complex interrelationships between agents responsible for the modulation of gastrointestinal physiology.