Cholecystokinin is not a peripheral satiety signal in the dog

1985 ◽  
Vol 249 (6) ◽  
pp. G733-G738
Author(s):  
T. N. Pappas ◽  
R. L. Melendez ◽  
K. M. Strah ◽  
H. T. Debas
Keyword(s):  
Pancreatic Enzyme ◽  
Cerebral Ventricle ◽  
Gastric Distension ◽  
Dependent Manner ◽  
Gallbladder Contraction ◽  
Sham Feeding ◽  
Pancreatic Enzyme Secretion ◽  
Pancreatic Fistulas ◽  
Dose Dependent ◽  
Lateral Cerebral Ventricle

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)

Pancreatic polypeptide inhibits pancreatic enzyme secretion via a cholinergic pathway

1987 ◽  
Vol 253 (5) ◽  
pp. G706-G710 ◽  
Author(s):  
G. Jung ◽  
D. S. Louie ◽  
C. Owyang
Keyword(s):  
Pancreatic Polypeptide ◽  
Acetylcholine Release ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Dependent Manner ◽  
Amylase Release ◽  
Opioid Receptor Antagonists ◽  
Cholinergic Pathway ◽  
Pancreatic Enzyme Secretion ◽  
Dose Dependent

In rat pancreatic slices, rat pancreatic polypeptide (PP) or C-terminal hexapeptide of PP [PP-(31-36)] inhibited potassium-stimulated amylase release in a dose-dependent manner. The inhibition was unaffected by addition of hexamethonium but blocked by atropine. In contrast, PP(31-36) did not have any effect on acetylcholine- or cholecystokinin octapeptide-stimulated amylase release. In addition, when pancreatic slices were incubated with [3H] choline, PP(31-36) inhibited the potassium-evoked release of synthesized [3H] acetylcholine in a dose-dependent manner. The inhibitory action of PP was unaffected by adrenergic, dopaminergic, or opioid receptor antagonists. Thus PP inhibits pancreatic enzyme secretion via presynaptic modulation of acetylcholine release. This newly identified pathway provides a novel mechanism for hormonal inhibition of pancreatic enzyme secretion via modulation of the classic neurotransmitter function.

Physiological role and localization of cholecystokinin release in dogs

1986 ◽  
Vol 250 (4) ◽  
pp. G391-G397 ◽  
Author(s):  
S. J. Konturek ◽  
J. Tasler ◽  
J. Bilski ◽  
A. J. de Jong ◽  
J. B. Jansen ◽  
...  
Keyword(s):  
Protein Secretion ◽  
Pancreatic Secretion ◽  
Pancreatic Enzyme ◽  
Physiological Role ◽  
Amino Acid Mixture ◽  
Acid Mixture ◽  
Elevated Plasma ◽  
Pancreatic Enzyme Secretion ◽  
Pancreatic Fistulas ◽  
Dose Dependent

In dogs with pancreatic fistulas, meat feeding and intestinal perfusion with a sodium oleate or amino acid mixture increased pancreatic protein secretion to approximately 110, 100, and 50%, respectively, of the response to cholecystokinin (CCK) at a dose of 85 pmol X kg-1 X h-1. Plasma CCK response increased in these studies to approximately 100, 180, and 40%, respectively, of the value obtained with exogenous CCK, suggesting that, in addition to CCK, other neurohormonal factors contribute to pancreatic enzyme secretion in response to endogenous stimulants. Feeding and duodenal oleate or amino acids also stimulate the release of pancreatic polypeptide (PP), which may be involved in the control of pancreatic secretion in response to endogenous stimulants, including CCK. Perfusion of the intact intestine with graded amounts of oleate (0.5-16 mmol/h) produced dose-dependent increments in plasma CCK and pancreatic protein similar to those obtained with intravenous infusion of graded doses of CCK (0.85-255 pmol X kg-1 X h-1). Oleate perfusion of isolated Thiry loops (30 cm long) made of duodenojejunal (D-J) and ileal (I) segments also stimulated protein secretion but elevated plasma CCK only after perfusion of the D-J but not of the I loop. We conclude that 1) the endogenous CCK released by various luminal stimulants drives the pancreatic protein secretion; 2) the release of CCK is confined to the foregut; and 3) PP concomitantly released by various intestinal stimulants may contribute to the control of pancreatic secretion induced by endogenous CCK.

Postgastric satiety in the sham-feeding rat

1983 ◽  
Vol 244 (6) ◽  
pp. R872-R881 ◽  
Author(s):  
R. D. Reidelberger ◽  
T. J. Kalogeris ◽  
P. M. Leung ◽  
V. E. Mendel
Keyword(s):  
Gastric Emptying ◽  
Meal Size ◽  
Gastric Distension ◽  
Dependent Manner ◽  
Sham Feeding ◽  
Total Intake ◽  
Threshold Rate ◽  
Dose Dependent ◽  
Fasted Rats

A sham-feeding model using rats fitted with gastric and duodenal cannulas was employed to investigate the role of postgastric mechanisms of satiety in the short-term control of food intake. When fasted rats sham fed a liquid diet [Vivonex High Nitrogen (VHN), 0.5 kcal/ml], food drained freely from gastric fistulas, and mean first-meal size and 90-min intake increased more than threefold. Varying the rate of duodenal infusion of diet during sham feeding (0.06-0.44 kcal/min) decreased first-meal size and total intake in a dose-dependent manner. First meals ended when mean loads of 2-3 kcal had been delivered. The threshold rate (0.11 kcal/min) decreased meal size and total intake by more than 50%. When fasted rats consumed VHN to satiety with closed gastric fistulas, rate of gastric emptying of diet during feeding averaged 0.32 +/- 0.02 kcal/min and the load emptied by meal termination averaged 3.8 +/- 0.2 kcal. These results indicate that rates of gastric emptying of diet and loads delivered to the small intestine following ingestion of liquid food are sufficient to elicit postgastric satiety in the absence of gastric distension.

Physiological changes during thermoregulation and fever in urethan-anesthetized rats

1988 ◽  
Vol 255 (1) ◽  
pp. R73-R81 ◽  
Author(s):  
T. J. Malkinson ◽  
K. E. Cooper ◽  
W. L. Veale
Keyword(s):  
Interleukin 1 ◽  
Cerebral Ventricle ◽  
Arterial Blood ◽  
Dependent Change ◽  
Male Wistar Rats ◽  
Series Of Experiments ◽  
Dose Dependent ◽  
Conscious Animals ◽  
Maintain Body Temperature ◽  
Lateral Cerebral Ventricle

Adult male Wistar rats were anesthetized with urethan (1.5 g/kg). They were unable to maintain body temperature (Tb) in a warm (32 degrees C) or cool (9 degrees C) environment or at a laboratory room temperature of 22 degrees C. Tb was allowed to fall to 35.8, 34.5, or 33.3 degrees C, and prostaglandin E1 (PGE1, 400 ng) was delivered into a lateral cerebral ventricle. An immediate feverlike rise in Tb resulted, accompanied by vigorous shivering. Animals were vasoconstricted throughout. When Tb was raised to and maintained at 38.3 or 39.5 degrees C, animals also responded with a fever; however, the magnitude of the fever diminished as the starting Tb increased. In a series of experiments in which Tb was maintained (36.8-37.4 degrees C) by means of a heating pad, PGE1 delivered into a lateral cerebral ventricle or into the anterior hypothalamus caused a dose-dependent change in Tb, which was similar in time of onset, magnitude, and duration to that observed in conscious animals. This fever was accompanied by shivering and increased O2 uptake, heart rate, arterial blood pressure, respiratory rate, and intracranial pressure during the rising phase of the fever, and vasodilation of the paws occurred during defeveresence. Animals were also able to develop a dose-dependent rise in Tb in response to purified human interleukin 1.

Role of CCK in regulation of pancreaticobiliary functions and GI motility in humans: effects of loxiglumide

1991 ◽  
Vol 260 (2) ◽  
pp. G197-G206 ◽  
Author(s):  
W. E. Schmidt ◽  
W. Creutzfeldt ◽  
A. Schleser ◽  
A. R. Choudhury ◽  
R. Nustede ◽  
...  
Keyword(s):  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Gallbladder Contraction ◽  
Stool Weight ◽  
Gallbladder Volume ◽  
Fecal Fat ◽  
Pancreatic Enzyme Secretion ◽  
Fat Excretion ◽  
Gi Motility

To evaluate the physiological role of cholecystokinin (CCK) in humans, we studied the influence of the specific CCK receptor antagonist loxiglumide (CR 1505) on gallbladder contraction, pancreatic enzyme output, plasma CCK concentrations, mouth-to-cecum transit time (MCTT), stool weight, and fecal fat excretion. Infusion of CCK-8, producing CCK plasma levels of 10-12 pmol/l, decreased gallbladder volume to 21% of the initial volume (P less than 0.01) and increased bilirubin output 8- to 10-fold and pancreatic enzyme secretion 2- to 4-fold. Infusion of loxiglumide (10 mg.kg-1.h-1 iv) abolished CCK-8-stimulated enzyme and bilirubin output. Basal gallbladder volume increased 68% during loxiglumide infusion (P less than 0.001) and 137% (P less than 0.001) after 7 days of oral loxiglumide treatment (3 x 1.6 g/day). Gallbladder contraction and bilirubin output in response to the intraduodenal instillation of a liquid meal (382 kcal) was completely inhibited by loxiglumide; gallbladder volume even increased 45% postprandially during loxiglumide infusion (P less than 0.02) and 145% after long-term loxiglumide treatment (P less than 0.001). Meal-stimulated pancreatic enzyme output was diminished 46-53% after acute and 25-29% after chronic administration of loxiglumide. Meal-stimulated integrated plasma CCK-immunoreactive (CCK-ir) concentrations, determined by RIA, were 3.2-fold higher during loxiglumide infusion (P less than 0.02); plateau CCK levels were markedly elevated (10.1 +/- 1.4 vs. 3.7 +/- 0.5 pM). Plasma CCK-like bioactivity, measured by a sensitive bioassay, was identical to CCK-ir levels in the absence of loxiglumide; in the presence of loxiglumide, no circulating CCK-like bioactivity was detectable, indicating complete inhibition of plasma CCK. MCTT was augmented 24% (P less than 0.05). Oral treatment with loxiglumide increased stool weight 72% (P less than 0.01) and fecal fat excretion 186% (P less than 0.001). In conclusion, 1) meal-induced gallbladder contraction and fasting tone are primarily controlled by CCK; 2) the contribution of CCK to the intestinal phase of postprandial pancreatic enzyme secretion is 40-50%; 3) GI motility and absorption are partially controlled by CCK; and 4) postprandial CCK secretion is substantially augmented by loxiglumide via an unknown mechanism.

Physiological plasma concentrations of cholecystokinin stimulate pancreatic enzyme secretion and gallbladder contraction in man

Life Sciences ◽  
1985 ◽  
Vol 36 (6) ◽  
pp. 565-569 ◽  
Author(s):  
P.J.S.M. Kerstens ◽  
C.B.H.W. Lamers ◽  
J.B.M.J. Jansen ◽  
A.J.L. de Jong ◽  
M. Hessels ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Gallbladder Contraction ◽  
Pancreatic Enzyme Secretion

Pancreastatin inhibits pancreatic enzyme secretion by presynaptic modulation of acetylcholine release

1992 ◽  
Vol 262 (1) ◽  
pp. G113-G117 ◽  
Author(s):  
K. H. Herzig ◽  
D. S. Louie ◽  
K. Tatemoto ◽  
O. Y. Chung
Keyword(s):  
Acetylcholine Release ◽  
Pancreatic Enzyme ◽  
Exocrine Secretion ◽  
Enzyme Secretion ◽  
Neural Pathways ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Presynaptic Modulation ◽  
Pancreatic Enzyme Secretion ◽  
Pancreatic Fistulas

Pancreastatin (PST), a 49-amino acid polypeptide, inhibits endocrine and exocrine pancreatic functions. In this study, we examined the mechanism of the inhibitory action of PST on exocrine pancreatic secretion in the rat. In anesthetized rats prepared with pancreatic fistulas, intravenous administration of PST (500 pM.kg-1.h-1) completely inhibited 2-deoxyglucose (75 mg/kg)-stimulated amylase output to below basal levels. Because 2-deoxyglucose acts to stimulate the vagus, we assessed the ability of PST to inhibit carbachol-stimulated amylase release from isolated rat pancreatic acini. PST suppressed neither carbachol- nor cholecystokinin-stimulated amylase release, indicating that PST inhibits exocrine secretion via indirect mechanisms. To examine neural pathways for inhibition, we used pancreatic lobules to examine the action of PST on intrapancreatic neurons. Incubation of pancreatic lobules in 75 mM potassium buffer stimulated amylase release by a cholinergic pathway. PST dose dependently inhibited potassium-evoked amylase release, with maximal inhibition of 49.6 +/- 11%. In addition, when lobules were incubated with [3H]choline, PST inhibited KCl-stimulated release of synthesized [3H]acetylcholine by 43 +/- 5.7%. Other studies demonstrate that PST inhibits rat pancreatic enzyme secretion via presynaptic modulation of acetylcholine release.

Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

1990 ◽  
Vol 63 (03) ◽  
pp. 505-509 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaar
Keyword(s):  
Molecular Weight ◽  
Bone Mineral ◽  
Low Molecular Weight Heparin ◽  
Zinc Content ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Bone Mineral Mass ◽  
Bone Ash ◽  
Dose Dependent ◽  
Mineral Mass

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

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