Gastric distension is a physiologic satiety signal in the dog.

Gastric distension is thought to produce satiety, but whether this effect is seen during physiologic distension by food is unknown. The purpose of this study was to determine whether levels of gastric distension seen during a meal have a satiety effect and whether the nutrient value of the meal was important. Four dogs were prepared with gastric, duodenal, and esophageal fistulas. Physiologic distension was determined by allowing the animals to eat liquid nutrient diet until sated and measuring the volume consumed and the time it took to consume it (means 2000 ml in 4 min). To test the effect of gastric distension on satiety, distension was produced during sham feeding by infusions of either liquid nutrient, inert liquid (Karaya), or by a water-filled balloon. Lower degrees of distension were also tested to determine if a dose-response relationship existed. Balloon, inert, and nutrient distension all inhibited sham feeding dose-dependently. Peak inhibitions of sham feeding caused by physiologic gastric distension (balloon, inert, nutrient) were 69 +/- 5%, 67 +/- 12%, and 61 +/- 6%, respectively. In all cases, maximal distension terminated sham feeding before the end of the feeding period. The effect of gastric distension on feeding was not blocked by pretreatment with atropine (50 micrograms/kg). Thus, graded degrees of gastric distension, comparable to those seen during ingestion of a normal meal, produced graded inhibition of food intake by a noncholinergic mechanism and independent of the nutrient properties of the food.

Contrasting cholinergic dependence of pancreatic and gallbladder responses to cholecystokinin.

Cholinergic receptors for cholecystokinin (CCK) have been identified on neurons of the enteric nervous system, including those of the gallbladder. To determine whether any differences exist in the extent to which CCK action depends on muscarinic cholinergic receptors in the pancreas and gallbladder, 11 dogs with pancreatic and 7 dogs with biliary fistulas were given increasing doses of intravenous CCK-8 (15-250 ng X kg-1 X h-1) or intraduodenal sodium oleate (0.1-9 mmol/h) with and without atropine pretreatment. Pancreatic protein response to CCK-8 was dose dependent, reaching a maximal of 448 +/- 76 mg/15 min at the highest dose. Atropine pretreatment caused nonsignificant reduction in the response to the lowest dose but had no effect on the responses to the other doses, with the response to the highest dose of CCK being 473 +/- 82 mg/15 min. In contrast, gallbladder contraction as measured by bile fistula bilirubin output was very sensitive to inhibition by atropine. Bilirubin responses to 16, 32, 62.5, 125, and 250 ng X kg-1 X h-1 were 14 +/- 5, 18 +/- 5, 28 +/- 5, 36 +/- 6, and 52 +/- 12 mg/h, respectively, without atropine and 0 +/- 0, 6 +/- 2, 7 +/- 2, 18 +/- 4, and 18 +/- 4 mg/h with atropine pretreatment. Similarly, pancreatic responses to sodium oleate infusion were less susceptible to inhibition by atropine than were the gallbladder responses. With respect to pancreatic protein secretion, the response to only the lowest dose of sodium oleate was significantly inhibited by atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactions of vasoactive intestinal polypeptide and cholecystokinin octapeptide on the control of gallbladder contraction.

The gallbladder is supplied by three types of vagal fibers: cholinergic, cholecystokinin (CCK)-ergic, and vasoactive intestinal polypeptide (VIP)-ergic. Most previous studies on the interaction of VIP and CCK on gallbladder contraction have been in vitro. In this study we evaluate this interaction more fully in vivo using six dogs with chronic bile fistula. Dose-response curves were constructed to CCK-8 alone and to VIP alone. The effect of graded doses of VIP on maximal response to CCK-8 was also studied. CCK-8 caused the expected dose-related stimulation of gallbladder contraction, while graded doses of VIP had the opposite effect. VIP also caused a dose-related inhibition of the maximal response to CCK-8, decreasing bilirubin output from 39 +/- 8 to 15 +/- 3 mg/hr (p less than 0.05). The corollary to these findings is that gallbladder tone and contraction is regulated by the interplay of stimulatory cholinergic-CCK-ergic and inhibitory VIP-ergic fibers. Further, a plausible explanation for the variable effects of vagotomy on gallbladder contraction is that variable proportions of these opposing fibers are cut.

Cholecystokinin is not a peripheral satiety signal in the dog.

The doses of cholecystokinin (CCK) that have been shown to cause satiety after peripheral administration are pharmacological and whether "physiological" doses of exogenous CCK or endogenously released CCK have a satiety effect is not known. The purpose of the present study is threefold: to compare the potency of endogenous and exogenous CCK for their satiety, cholecystokinetic, and pancreozyminic actions; to determine whether small doses of CCK in the presence of gastric distension cause satiety; and to test the satiety effect of CCK administered centrally into the lateral cerebral ventricle. Dogs were prepared with cerebroventricular guides and esophageal and duodenal fistulas (n = 4), with chronic bile fistulas (n = 8), and chronic pancreatic fistulas (n = 7). Satiety effect was quantified in the esophageal fistula dog by the amount of blenderized food sham fed within 7.5 min. Duodenal perfusion of fat, used as a releaser of endogenous CCK, stimulated pancreatic protein, and gallbladder contraction with D50 values of 1.5 and 0.3 mmol/h, respectively, but had no effect on the volume sham fed (316 +/- 82 ml/min without and 371 +/- 41 ml/min with the maximal dose of sodium oleate infused). The D50 values of CCK-8 (pmol X kg-1 X h-1) for satiety and for stimulation of pancreatic enzyme secretion and gallbladder contraction were 440, 120, and 22, respectively. Injection of CCK-8 into the lateral cerebral ventricle inhibited sham feeding in a dose-dependent manner. We conclude that duodenal fat in doses producing maximal gallbladder and pancreatic stimulation has no satiety effect in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)