T. Richard Houpt

Satiety elicited by cholecystokinin in intact and vagotomized rats

Abstract The effect of exogenous cholecystokinin and gastric loads of substances shown to release endogenous cholecystokinin were investigated in rats. Intraperitoneal injection of cholecystokinin and caerulein produced a significant suppression of food but not water intake. Phenylalanine (the L but not the D isomer), egg yolk and 0.1 N HCl but not MgSO 4 depressed feeding in the fasted rats. This satiety effect does not seem to be mediated via the vagus nerve, as suppression of food-intake was observed after subdiaphragmatic vagotomy. Blocking of pancreatic enzyme secretion does not prevent cholecystokinin-induced satiety.

The sites of action of cholecystokinin in decreasing meal size in pigs

The synthetic octapeptide of cholecystokinin (CCK-8) was infused at the rate of 67 ng/kg-minute into the jugular vein, carotid artery, portal vein, gastric branch of the splenic artery, and aortic artery both craniad and caudad to the origins of the cranial mesenteric and coeliac arteries of 39 young female pigs. Jugular, carotid and cranial erotic infusions resulted in significant reduction of meal size respectively to 65, 67 and 71% of control meal size (p less than 0.05). Gastric artery infusion resulted in a significant increase of meal size to 122% of control meal size (p less than 0.05). Portal vein and caudal aortic artery infusions had no significant effects on meal size. The results were interpreted as indicating a major site of action of CCK in reducing meal size in the bed of the cranial mesenteric or coeliac arteries, but excluding the stomach and liver.

Gastric emptying and cholecystokinin in the control of food intake in suckling rats

The rate of gastric emptying was determined in three-day old suckling rats. The gastric loads were given by gavage, and, after from 5 to 100 min, emptying was determined by removing the stomach and weighing the contents. Results were expressed as percentage of load still remaining in the stomach at one hour. The gastric loads in increasing order of speed of emptying were 1.0 M Na acetate, heavy cream, 0.5 M NaCl, milk, corn oil, 0.15 M lactose, 0.3 M glucose, 0.15 M NaCl, acidic water, and water. The rate of emptying was compared to the effectiveness in previous experiments of the same gastric loads in depressing intake. There was no significant correlation between rate of gastric emptying of the loads and their effectiveness in producing satiety. The octapeptide of cholecystokinin (80 Ivy dog units or 2.7 micrograms/kg i.p.) significantly depressed intake (measured as weight gain) of suckling rats of 1 1/2 hours, but the same dose did not slow gastric emptying. These findings indicate that rate of gastric emptying does not determine satiety in the suckling rat.

Water deprivation, plasma osmolality, blood volume, and thirst in young pigs.

When deprived of both drinking water and food, pigs failed to develop the hyperosmolality usually expected with dehydration. In further studies 12 pigs were deprived of drinking water and food, and the effects were compared with data from nondeprived pigs, pigs water deprived but with food available, and pigs with water but no food. When food was eaten during water deprivation, plasma osmolality rose to levels sufficient to stimulate drinking. During water and food deprivation, plasma osmolality failed to rise, even over 24 h, and usually fell. Blood volume changes were calculated from packed cell volume and plasma protein data, and it was found that blood volume fell significantly when both food and water were withheld, but not when only water was withheld. It appears that the conditions of deprivation determine the proportions of thirst stimulation that can be attributed to plasma hypertonicity and to hypovolemia.

The physiological determination of meal size in pigs

As a meal is being eaten, rapid inhibitory signals to the central nervous system (CNS) determine what the size of that meal will be. These signals are initiated by food in the alimentary canal, and inhibition of further eating results when sufficient food has been ingested to correct the nutritional deficit. The match between size of meal and nutritional deficit is, however, only a rough approximation. Control of meal size in pigs will be the primary subject of this paper; however, similar studies on ruminants and equids will be considered briefly.

Recovery from disordered drinking by vagotomized rats.

Abstract Within 8 weeks after bilateral subdiaphragmatic vagotomy, rats failed to respond to 3 stimuli of thirst: water consumption in absence of food, cellular dehydration produced by hypertonic NaCl, and beta-adrenergic activation using isoproterenol. Sixteen weeks post-surgery, however, these deficits in drinking behavior disappeared. Eight weeks after surgery, for example, following intragastric loads of 5% NaCl at 1 ml/100 g body weight, vagotomized rats drank 2.3 ± 0.3 ml water; their sham-operated controls drank 17.4 ± 1.6 ml. The corresponding values 16 weeks post-surgery were 17.4 ± 0.7 for the vagotomized rats and 17.9 ± 0.7 ml for the laparotomized controls. When isoproterenol (0.05 mg/100 g) was injected, for the initial tests vagotomized rats and their controls drank 3.2 ± 0.3 ml and 15.8 ± 0.8 ml water, respectively, and the corresponding values 16 weeks post-surgery were 15.8 ± 0.7 ml and 14.9 ± 0.7 ml, respectively. There was no recovery of efferent vagal function so recovery of drinking was probably not due to nerve regeneration.

Stimuli of thirst in donkeys (Equus asinus)

A study of the stimuli of thirst was conducted on six feral donkeys. Donkeys were found to be stimulated to drink by overnight water deprivation, by the diuretic furosemide, and by hypertonic saline infusion, all in the absence of heat stress or work. Donkeys compensate accurately for the fluid deficit caused by overnight water deprivation. After 19 hr without water, they drank 8.8 +/- 2.4 (mean +/- SE) liters within 60 min. Their undeprived overnight intake was 8.4 +/- 1.5 liters. However, latency was longer and water intake was less than that of ponies with the same changes in blood parameters, suggesting that donkeys have a higher thirst threshold than ponies. Further, plasma volume fell less in donkeys, but osmotic changes were similar to those reported in ponies exposed to the same deprivation. Donkeys infused with 250 ml of 15% NaCl drank 0.7 +/- 0.6 liters of water within 45 min, and osmolality increased from 287 to 297 mosmol/kg water; they drank no water in the same time period when infused with 250 ml 0.9% NaCl (p less than 0.05). Donkeys injected IV with 2 mg/kg furosemide drank 3.8 +/- 1.1 liters within 3 hr. Plasma protein increased from 6.9 to 7.8 g/dl. When injected with 0.9% NaCl they drank 1.0 +/- 0.5 liters (p less than 0.05). In sum, the positive thirst responses of these donkeys to cellular and extracellular dehydration were similar to those earlier demonstrated in ponies, but the results suggest a less sensitive response, albeit combined with a better internal defense of blood volume.

A rapid feedback signal is not always necessary for termination of a drinking bout

When a pig is deprived of drinking water, a deficit of body water develops that is corrected when the pig drinks to satiation. If food is available during the deprivation, the stimulus to drinking is plasma hyperosmolality. Because of the delay in correction of plasma hyperosmolality as ingested water is slowly absorbed, it has been thought that a rapid inhibitory signal from the digestive tract is necessary to prevent overdrinking. This concept was tested by measuring changes in plasma osmolality before and during drinking after such deprivation and also after infusion of hypertonic saline. As drinking began, there was a rapid fall of plasma osmolality to levels insufficient to drive drinking by the time drinking ended. This fall of plasma hyperosmolality to subthreshold levels while the pig is drinking seems to make a rapid inhibitory control signal from the digestive tract unnecessary to terminate the drinking bout under these conditions.When a pig is deprived of drinking water, a deficit of body water develops that is corrected when the pig drinks to satiation. If food is available during the deprivation, the stimulus to drinking is plasma hyperosmolality. Because of the delay in correction of plasma hyperosmolality as ingested water is slowly absorbed, it has been thought that a rapid inhibitory signal from the digestive tract is necessary to prevent overdrinking. This concept was tested by measuring changes in plasma osmolality before and during drinking after such deprivation and also after infusion of hypertonic saline. As drinking began, there was a rapid fall of plasma osmolality to levels insufficient to drive drinking by the time drinking ended. This fall of plasma hyperosmolality to subthreshold levels while the pig is drinking seems to make a rapid inhibitory control signal from the digestive tract unnecessary to terminate the drinking bout under these conditions.

Gastric pressures in pigs during eating and drinking

Pressures were measured with miniature transducers positioned within the gastric lumen of six young pigs, 20-40 kg, eating and drinking operantly. The pigs were free to move about, lie down, sleep, eat, and drink without disturbance. 1) At the end of 4-5-h fasts (with no drinking), mean pressure within the stomach was 12 cm H2O, then rose during 22-min eating bouts to 22 cm H2O. 2) At the end of 16-18-h periods of food and water deprivation, intragastric pressure was 9 cm H2O. When water was drunk, pressures rose only to 13 cm H2O, then fell. When food was then eaten, pressures rose during 29-min meals to 22 cm H2O. 3) During spontaneous eating and drinking, intermeal pressures were maintained at 22-25 cm H2O, fell by 4-5 cm H2O just as eating or drinking began, then rose slowly, but only to the preingestive pressure level by the end of the bout. These results indicate that during spontaneous eating and drinking, gastric distention per se plays a smaller direct role in causing satiety than it does during meals ingested after a period of food deprivation.

The mechanism and significance of pentagastrin-stimulated water intake in the pig

The role of gastric secretion in drinking was investigated. Treatment of pigs with cimetidine (300 mg IV), which inhibits gastric secretion, did not change the level of feed or water intake, or alter the temporal relationship between eating and drinking. Gastric infusions of 0.15 M HCl (5 ml.kg-1.h-1) did not increase drinking. Pentagastrin infusion (0.05 microgram.kg-1.min-1) increased water intake in some, but not all pigs during a 1-hour infusion. Plasma protein levels increased significantly during 1-hour pentagastrin infusions (0.05 microgram.kg-1.min-1), indicating an estimated fall in blood volume of 2.5%. Captopril (1.75 mg/kg IV), which blocks the renin-angiotensin system, abolished pentagastrin-stimulated drinking. It was concluded that gastric secretion does not play a direct role in normal, periprandial drinking but that in pigs the renin-angiotensin system is involved in pentagastrin-stimulated drinking.