Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats

1994 ◽  
Vol 267 (4) ◽  
pp. R901-R908 ◽  
Author(s):  
R. D. Reidelberger ◽  
G. Varga ◽  
R. M. Liehr ◽  
D. A. Castellanos ◽  
G. L. Rosenquist ◽  
...  
Keyword(s):  
Food Intake ◽  
Pancreatic Enzyme ◽  
Free Access ◽  
Amylase Secretion ◽  
Receptor Antagonists ◽  
Feeding Experiments ◽  
Pancreatic Enzyme Secretion ◽  
Endocrine Mechanism ◽  
Access To Food ◽  
Cck Receptor Antagonists

A cholecystokinin monoclonal antibody (CCK MAb) was used to immunoneutralize CCK to test the hypothesis that CCK produces satiety by an endocrine mechanism. We first characterized the effects of CCK MAb on pancreatic secretion. Conscious rats with jugular vein and bile-pancreatic duct cannulas received CCK MAb or control antibody intravenously 30 min before a 2-h maximal dose of CCK-8 (200 pmol.kg-1.h-1 i.v.) or access to food. CCK MAb caused dose-related inhibition of amylase secretion. CCK MAb (2 mg/kg) completely blocked the response to CCK-8 and inhibited the response to food by 89%. In feeding experiments, rats with free access to food received CCK MAb or control antibodies (2 mg/kg iv) 2 h after lights off. CCK MAb had no effect on 1.5- or 3.5-h food intake. Another group of rats received CCK MAb (4 mg/kg i.v.) or a combined injection of type A and type B CCK receptor antagonists devazepide and L-365,260 (1 mg/kg each i.v.). CCK MAb had no effect on feeding, whereas the receptor antagonists stimulated 1-, 2-, 3-, and 4-h intake by 62, 45, 43, and 29%. These results suggest that endogenous CCK stimulates pancreatic enzyme secretion at least partially by an endocrine mechanism and produces satiety by a nonendocrine mechanism.

Stimulus–secretion coupling in exocrine pancreas: possible role of calmodulin

1981 ◽  
Vol 59 (9) ◽  
pp. 994-1001 ◽  
Author(s):  
Seymour Heisler ◽  
Laurence Chauvelot ◽  
Diane Desjardins ◽  
Christiane Noel ◽  
Herman Lambert ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Pancreatic Enzyme ◽  
Antidepressant Drugs ◽  
Enzyme Secretion ◽  
Pancreatic Acinar Cells ◽  
Secretory Process ◽  
Amylase Secretion ◽  
Enzyme Release ◽  
Mediated Effects ◽  
Pancreatic Enzyme Secretion

Many calcium-mediated effects in mammalian cells may be activated by calcium-calmodulin stimulated enzymes. These effects are inhibited by various antidepressant drugs which bind to and inactivate calmodulin. In the current study, calmodulin was identified by affinity chromatography and gel electrophoresis in the cytoplasm of dispersed rat pancreatic acinar cells. Its role in enzyme secretion was assessed by evaluating the effects of various antidepressant drugs on the enzyme secretory process. Chlorpromazine, trifluoperazine, thioridazine, chlorprothixene and amitriptyline inhibited amylase secretion stimulated by carbacol, A-23187, and cholecystokinin-pancreozymin but not that elicitied by dibutyryl cyclic AMP secretin or vasoactive intestinal peptide (VIP). Haloperidol, sulpiride, phenobarbital, and ethanol were without effect on secretagogue-stimulated enzyme release. Only those agents which blocked secretion also inhibited 45Ca release stimulated by carbachol from isotope preloaded cells. The data suggest that calmodulin may have a functional role in pancreatic enzyme secretion.

Bovine pancreatic polypeptide as an antagonist of muscarinic cholinergic receptors

1987 ◽  
Vol 252 (3) ◽  
pp. G384-G391
Author(s):  
G. Z. Pan ◽  
L. Lu ◽  
J. M. Qian ◽  
B. G. Xue
Keyword(s):  
Pancreatic Polypeptide ◽  
Pancreatic Enzyme ◽  
Cholinergic Receptors ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Enzyme Release ◽  
Muscarinic Cholinergic Receptors ◽  
Bovine Pancreatic Polypeptide ◽  
Pancreatic Enzyme Secretion ◽  
Muscarinic Cholinergic

In dispersed acini from rat pancreas, it was found that bovine pancreatic polypeptide (BPP) and its C-fragment hexapeptide amide (PP-6), at concentrations of 0.1 and 30 microM, respectively, could significantly inhibit amylase secretion stimulated by carbachol (P less than 0.01 or 0.05, respectively), and this inhibition by BPP was dose dependent. 45Ca outflux induced by carbachol was also inhibited by BPP or PP-6, but they had no effect on cholecystokinin octapeptide- (CCK-8) or A23187-stimulated 45Ca outflux. BPP was also capable of displacing the specific binding of [3H]quinuclidinyl benzilate to its receptors, and it possessed a higher affinity (ki 35 nM) than carbachol (Ki 1.8 microM) in binding with M-receptors. It is concluded from this study that BPP acts as an antagonist of muscarinic cholinergic receptors in rat pancreatic acini. In addition, BPP inhibited the potentiation of amylase secretion caused by the combination of carbachol plus secretin or vasoactive intestinal peptide. This may be a possible explanation of the inhibitory effect of BPP on secretin-induced pancreatic enzyme secretion shown in vivo, since pancreatic enzyme secretion stimulated by secretin under experimental conditions may be the result of potentiation of enzyme release produced by the peptide in combination with a cholinergic stimulant.

scholarly journals Effects of infusions of lysine, leucine and ammonium chloride into the hepatic portal vein of chickens on voluntary food intake

1987 ◽  
Vol 58 (2) ◽  
pp. 325-331 ◽  
Author(s):  
Audrey A. Rusby ◽  
J. M. Forbes
Keyword(s):  
Food Intake ◽  
Portal Vein ◽  
Ammonium Chloride ◽  
Jugular Vein ◽  
Free Access ◽  
Delayed Effect ◽  
Hepatic Portal Vein ◽  
Hepatic Portal ◽  
Access To Food ◽  
Portal Infusion

1. Adolescent cockerels of a laying strain were prepared with catheters whose tip lay in the hepatic portal vein, to study the effect of 3-h infusions of nutrients on food intake.2. Lysine, infused into the hepatic portal vein at rates of 150–450 mg/3 h reduced 3-h food intake by up to 58%, for a period of 6 h in previously starved birds, but had no effect on birds allowed free access to food. Infusions made into the jugular vein had no effect, suggesting a role for the liver in monitoring lysine levels.3. Portal infusion of leucine had a delayed effect while ammonium chloride, infused at isomolar rates to those of the lysine infusions, had very little effect on intake.4. The results support the concept of liver sensitivity to amino acids, but the mode of action is not clear; it appears not to be via the effects of ammonia.

The Effect of Centrally Administered CCK-Receptor Antagonists on Food Intake in Rats

1997 ◽  
Vol 61 (6) ◽  
pp. 823-827 ◽  
Author(s):  
Eric S Corp ◽  
Michael Curcio ◽  
James Gibbs ◽  
Gerard P Smith
Keyword(s):  
Food Intake ◽  
Receptor Antagonists ◽  
Cck Receptor Antagonists

Early Dissociation of Protein Synthesis and Amylase Secretion Following Hormonal Stimulation of the Pancreas

1974 ◽  
Vol 52 (2) ◽  
pp. 198-205 ◽  
Author(s):  
R. Mongeau ◽  
Y. Couture ◽  
J. Dunnigan ◽  
J. Morisset
Keyword(s):  
Protein Synthesis ◽  
Incubation Medium ◽  
Single Injection ◽  
Pancreatic Enzyme ◽  
Amylase Secretion ◽  
Hormonal Stimulation ◽  
Pancreatic Enzyme Secretion ◽  
Metabolic Conditions

The secretion of the various pancreatic enzymes can be increased by hormonal and cholinergic stimulation. However, it is not yet clear among the different investigators if their synthesis remains constant or can be modified according to different metabolic conditions. The secretion and synthesis of the pancreatic proteins were then studied in parallel to evaluate if secretion triggers synthesis or both phenomenons are controlled by separate mechanisms.The approach for these studies consists mainly in a combination of in vivo and in vitro experiments. The stimulants were injected in vivo and the pancreatic secretions were collected for different periods of time. The animals were then sacrificed and protein synthesis was measured in vitro along with the amylase secreted into the incubation medium. The results show that protein synthesis is decreased during the first 15 min after a single injection or infusion of both cholecystokinin–pancreozymin (CCK–PZ) and secretin. This reduction was associated with an increase in amylase secreted into the incubation medium. However, at 30 min after the hormonal stimulation, protein synthesis is increased while secretion into the incubation medium had returned to control levels. This increase in protein synthesis lasts for at least 1 h. These results strongly suggest that pancreatic enzyme secretion and synthesis are dissociated in the early minutes following hormonal stimulation.

Stimulus-secretion coupling in exocrine pancreas: role of protein carboxyl methylation

1981 ◽  
Vol 240 (3) ◽  
pp. G199-G205
Author(s):  
V. Povilaitis ◽  
C. Gagnon ◽  
S. Heisler
Keyword(s):  
Pancreatic Enzyme ◽  
Cellular Protein ◽  
Secretory Response ◽  
Receptor Interaction ◽  
Amylase Secretion ◽  
Amylase Release ◽  
Carboxyl Methylation ◽  
Calcium Requirement ◽  
Pancreatic Enzyme Secretion

The role of protein carboxyl methylation in amylase secretion from incubated rat pancreatic lobules was assessed. All the components of the carboxyl methylation system, protein carboxyl methylase, methyl-acceptor protein substrates, and protein methylesterase, were found in the rat pancreas. Protein carboxyl methylation is stimulated by both pancreozymin and carbachol at concentrations that are equally effective in stimulating amylase release. The secretagogue-enhanced increase in protein carboxyl methylation was concomitant with the onset of the secretory response. These responses were blocked by the receptor antagonists, dibutyryl cGMP and atropine. Inhibitors of protein carboxyl methylase inhibited carboxyl methylation stimulated by pancreozymin but did not affect the secretory response to the hormone. Ethyleneglycol-bis-(beta-aminoethylether)-N-N'-tetraacetic acid blocked protein carboxyl methylation and amylase release, indicating that extracellular calcium was essential for both processes. The presence or absence of calcium did not alter the enzyme activity in lobule homogenates. The data suggest that only a small part of the total cellular protein carboxyl methylation activity is directly involved in pancreatic enzyme secretion. Like the calcium requirement in secretion, protein carboxyl methylation also lies distal to the stimulant-receptor interaction.

Prostaglandin E2 inhibits secretagogue-induced enzyme secretion from rat pancreatic acini

1991 ◽  
Vol 260 (5) ◽  
pp. G711-G719
Author(s):  
J. Mossner ◽  
R. Secknus ◽  
G. M. Spiekermann ◽  
C. Sommer ◽  
M. Biernat ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Pancreatic Enzyme ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Binding Studies ◽  
Pancreatic Acini ◽  
Inositol 1,4,5 Trisphosphate ◽  
Pancreatic Enzyme Secretion ◽  
Hcl Secretion ◽  
Specific Receptors

Prostaglandins of the E type may have a potential role in pancreatic physiology and pathophysiology. Because prostaglandins of the E type inhibit HCl secretion in parietal cells via a specific receptor by inhibition of adenylylcyclase, we studied whether a similar mechanism exists in the exocrine pancreas. Isolated rat pancreatic acini were incubated with various concentrations of secretagogues, such as cholecystokinin-octapeptide (CCK-8), bombesin, carbachol, and vasoactive intestinal peptide (VIP), in the absence or presence of prostaglandin E2 (PGE2), and amylase secretion was measured. For receptor binding studies, acini and pancreatic membranes were incubated with [3H]PGE2 and either unlabeled PGE2 or other types of prostaglandins. PGE2 (10(-13) to 10(-5) M) did not inhibit basal amylase secretion. However, CCK-8-stimulated secretion was significantly inhibited. Stimulation of secretion by bombesin, carbachol, VIP, and secretin was also inhibited by PGE2, but not as pronounced as CCK-8-stimulated secretion. The formation of inositol 1,4,5-trisphosphate induced by CCK-8 was markedly inhibited by simultaneous incubation with PGE2. Furthermore, PGE2 slightly but significantly reduced the CCK-8-induced efflux of 45Ca2+ from prelabeled acini. Intact acini and a membrane fraction bound [3H]PGE2 and this function could be equally competed by either unlabeled PGE2 or PGE1 in contrast to less-related prostaglandins such as PGF2 alpha, PGD2, and prostacyclin. We conclude that prostaglandins of the E type inhibit pancreatic enzyme secretion stimulated by various secretagogues. This function is mediated via specific receptors for PGE. With regard to CCK-8-stimulated secretion this function may be mediated by an inhibition of formation of inositol 1,4,5-trisphosphate.

Biochemical Reactions Involved in Pancreatic Enzyme Secretion. I. Activation of the Adenylate Cyclase Complex

1974 ◽  
Vol 52 (2) ◽  
pp. 174-182 ◽  
Author(s):  
A. R. Beaudoin ◽  
C. Marois ◽  
J. Dunnigan ◽  
J. Morisset
Keyword(s):  
Adenylate Cyclase ◽  
Pancreatic Enzyme ◽  
Pancreatic Tissue ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Biochemical Reactions ◽  
Pancreatic Enzyme Secretion

Pancreatic amylase secretion was studied using an in vitro system. Secretion was increased by urecholine and cholecystokinin–pancreozymin (CCK–PZ). Addition of tetracaine and dibucaine to the medium abolished secretion stimulated by urecholine and decreased by 75% that stimulated by CCK–PZ. In contrast, an increase in enzyme secretion was observed after dibutyryl cyclic AMP; this was potentiated by tetracaine added to the medium. Oxygen uptake by pieces of pancreatic tissue was not affected by tetracaine. Adenylate cyclase activity, increased in vitro when CCK–PZ was added to a pancreas homogenate, was inhibited by 15% by tetracaine at 2 mM and by 67.5% at the 10 mM concentration.From data known on biochemical reactions associated with the process of secretion and the results described in the present paper, we propose a model for the activation of the pancreatic adenylate cyclase complex. Associated to the depolarization of the acinar cell plasma membrane by urecholine and CCK–PZ and an inward movement of sodium and calcium, there is an immediate rise in adenylate cyclase activity within 10 s which is timed with the initiation of amylase secretion.

NEUROANATOMICAL STUDY OF OBESE AND NON-OBESE HYPOTHALAMIC MONKEYS IN RELATION TO FOOD INTAKE, LOCOMOTOR ACTIVITY, AND TEMPERATURE REGULATION

1962 ◽  
Vol 40 (1) ◽  
pp. 1185-1193
Author(s):  
Louis J. Poirier ◽  
Anne-Marie Mouren-Mathieu ◽  
Claude-Lise Richer
Keyword(s):  
Food Intake ◽  
Central Area ◽  
Free Access ◽  
Optic Chiasma ◽  
Mammillary Bodies ◽  
Hypothalamic Nuclei ◽  
Bilateral Lesions ◽  
Access To Food ◽  
Bilateral Destruction ◽  
Maintain Body Temperature

Obesity, hypoactivity, and an impairment of ability to maintain body temperature in moderate cold were encountered in combination, or separately, following experimental bilateral destruction between the optic chiasma and the mammillary bodies in the hypothalamus. An impairment in the ability to regulate temperature against cold was present in all six obese monkeys of this series following lesions which destroyed extensively the periventricular system and the paraventricular and dorsomedial hypothalamic nuclei. This was associated with hypoactivity in two out of three obese animals in which this function was studied. Obesity occurred without any increase in food intake in three animals in which the diet was controlled; only one of these showed a slight hyperphagia when free access to food was permitted. One non-obese animal showed marked hyperactivity associated with a voracious appetite and an inability to regulate against cold following small bilateral lesions in the central area of the hypothalamus.

Comparative effects of CCK receptor antagonists on rat pancreatic secretion in vivo

1989 ◽  
Vol 256 (1) ◽  
pp. G150-G157 ◽  
Author(s):  
M. Niederau ◽  
C. Niederau ◽  
G. Strohmeyer ◽  
J. H. Grendell
Keyword(s):  
Pancreatic Secretion ◽  
Rank Order ◽  
Amylase Secretion ◽  
Receptor Antagonists ◽  
Pancreatic Acini ◽  
Cck Receptors ◽  
Competitive Kinetics ◽  
Cck Receptor Antagonists

The present experiments evaluate in vivo effects of recently described cholecystokinin (CCK) receptor antagonists on rat pancreatic secretion. Pancreaticobiliary secretion was studied after bile duct cannulation in anesthetized rats. After two basal 10-min fractions were selected, secretion was stimulated by intravenous caerulein (0.1-30.0 micrograms/kg) or secretin, and collected for seven further 10-min fractions. Peptide antagonists (CR 1409, CR 1392, and CR 1505) and nonpeptide antagonists (asperlicin and L364,718) were given intravenously 10 min before agonists. Increasing doses of antagonists gradually reduced secretion of protein and enzymes stimulated by submaximal and maximal doses of caerulein. The antagonists did not alter nonstimulated or secretin-stimulated secretion, indicating their specificity for the CCK receptor. Except for proglumide and asperlicin, all antagonists were able to abolish caerulein-stimulated pancreatic secretion, as evaluated by the mean integrated 1-h response to a near-maximal dose of caerulein. The caerulein dose-response curve was gradually shifted to the right by increasing doses of CR 1409, indicating competitive-like kinetics. Inhibition of secretion due to supramaximal doses of caerulein, however, could be reversed by doses of CR 1409 smaller than expected from extrapolating truely competitive kinetics from an in vitro situation to the in vivo situation. The rank order of potency of the compounds to antagonize caerulein-stimulated secretion in vivo agreed with their relative potencies to antagonize caerulein-stimulated amylase secretion from pancreatic acini in vitro as well as with their affinity to bind to peripheral CCK receptors in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

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