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Regulation of gastric emptying in humans by cholecystokinin.
R A Liddle, … , C K Conrad, J A Williams
R A Liddle, … , C K Conrad, J A Williams
Published March 1, 1986
Citation Information: J Clin Invest. 1986;77(3):992-996. https://doi.org/10.1172/JCI112401.
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Regulation of gastric emptying in humans by cholecystokinin.

Abstract

In the present study we used a bioassay system for measuring plasma cholecystokinin (CCK) to evaluate whether CCK has a physiologic role in regulating gastric emptying in humans. Plasma CCK levels and gastric emptying after ingestion of a mixed liquid meal were determined in five normal male volunteers. Fasting CCK levels averaged 0.8 +/- 0.1 pM and increased to 6.5 +/- 1.0 pM within 10 min of drinking the mixed meal. CCK levels remained elevated for up to 90 min. Gastric emptying after a meal was slow; at the end of the 90 min 68% of the original volume remained in the stomach. The rate of gastric emptying of water was then measured in the same individuals with a simultaneous infusion of either saline, or one of two doses of CCK (12 pmol/kg per h and 24 pmol/kg per h). With the saline infusion, plasma CCK levels did not increase above basal and gastric contents emptied rapidly. At the end of 90 min only 7% of the original volume remained in the stomach. The lower dose of CCK resulted in a plasma level of 3.4 pM which both reproduced the average postprandial plasma level and caused a significant delay in gastric emptying. The higher dose of CCK achieved plasma levels of 8 pM and resulted in a delay in gastric emptying that was similar to that seen with the mixed meal. Since exogenous CCK at concentrations which occur postprandially delays gastric emptying, we conclude that CCK is a physiologic regulator of gastric emptying.

Authors

R A Liddle, E T Morita, C K Conrad, J A Williams

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C Kreiss, W Schwizer, J Borovicka, JB Jansen, C Bouloux, R Pignol, A Bischof-Delaloye, M Fried 		Regulatory Peptides 1998
Fatty acids stimulate cholecystokinin secretion via an acyl chain length-specific, Ca2+-dependent mechanism in the enteroendocrine cell line STC-1
JT McLaughlin, RB Lomax, L Hall, GJ Dockray, DG Thompson, G Warhurst 		The Journal of Physiology 1998
Evidence for a lipid specific effect in nutrient induced human proximal gastric relaxation
JT McLaughlin, LE Troncon, J Barlow, LJ Heggie, DG Thompson 		Gut 1998
Chronic Pancreatitis
CS Pitchumoni 		Journal of Clinical Gastroenterology 1998
Gastrin, Cholecystokinin, and Somatostatin in a Laboratory Experiment of Patients With Functional Dyspepsia:
BH Jonsson, K Uvnas-Moberg, T Theorell, R Gotthard 		Psychosomatic medicine 1998
Cholecystokinin Decreases Intestinal Hexose Absorption by a Parallel Reduction in SGLT1 Abundance in the Brush-Border Membrane
AJ Hirsh, CI Cheeseman 		The Journal of biological chemistry 1998
Effect of CCK on proximal gastric motor function in humans
JW Straathof, B Mearadji, CB Lamers, AA Masclee 		AJP Gastrointestinal and Liver Physiology 1998
Inhibition of gastric emptying in response to intestinal lipid is dependent on chylomicron formation
HE Raybould, JH Meyer, Y Tabrizi, RA Liddle, P Tso 		American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 1998
Störungen der Ösophagus- und Magenmotilität bei Kindern
G Stacher, U Weber 		European Surgery 1997
Cholecystokinin-A receptor antagonists: therapies for gastrointestinal disorders
M D'Amato, LC Rovati 		Expert Opinion on Investigational Drugs 1997
Role of cholecystokinin in the regulation of liquid gastric emptying and gastric motility in humans: studies with the CCK antagonist loxiglumide
W Schwizer, J Borovicka, P Kunz, R Fraser, C Kreiss, M D'Amato, G Crelier, P Boesiger, M Fried 		Gut 1997
Gastric emptying following pylorus-preserving whipple and duodenum-preserving pancreatic head resection in patients with chronic pancreatitis
MW Müller, H Friess, HG Beger, J Kleeff, B Lauterburg, B Glasbrenner, RL Riepl, MW Büchler 		The American Journal of Surgery 1997
Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans
MA Nauck, U Niedereichholz, R Ettler, JJ Holst, C Ørskov, R Ritzel, WH Schmiegel 		American journal of physiology. Endocrinology and metabolism 1997
Gastric emptying in OLETF rats not expressing CCK-A receptor gene
E Shoji, T Okumura, S Onodera, N Takahashi, K Harada, Y Kohgo 		Digestive Diseases and Sciences 1997
Intraduodenal lipid does not inhibit acid secretion in OLETF rats not expressing CCK-A receptor gene
E Shoji, T Okumura, Y Kohgo 		Digestive Diseases and Sciences 1996
Camostate- and caerulein-induced delay of gastric emptying in the rat: effect of CCK receptor antagonists
G Varga, C Scarpignato 		European Journal of Pharmacology 1996
Oral glucose ingestion stimulates cholecystokinin release in normal subjects and patients with non-insulin-dependent diabetes mellitus
H Hasegawa, H Shirohara, Y Okabayashi, T Nakamura, M Fujii, M Koide, M Otsuki 		Metabolism 1996
Methods in Neurosciences
V Rybin, HM Han, SF Steinberg 		Methods in Neurosciences 1996
Effect of lactic acid on postprandial plasma-glucose and -insulin responses in rats administered glucose solution
K Ebihara 		Nutrition Research 1996
Inhibitory effects of cholecystokinin on postprandial gastric myoelectrical activity
JD Chen, ZY Lin, S Parolisi, RW McCallum 		Digestive Diseases and Sciences 1995
Effects of cholestyramine on gallbladder and gastric emptying in obese and lean subjects
P Portincasa, AD Ciaula, V Palmieri, GP van Berge-Henegouwen, G Palasciano 		European Journal of Clinical Investigation 1995
Lipase Inhibition and Hormonal Status, Body Composition and Gastrointestinal Processing of a Liquid High-Fat Mixed Meal in Moderately Obese Subjects
ML Drent, C Popp-Snijders, HJ Adér, JB Jansen, EA Veen 		Obesity research 1995
Anterior, posterior, left anterior oblique, and geometric mean views in gastric emptying studies using a glucose solution
WT Phillips, CA McMahan, JC Lasher, MR Blumhardt, JG Schwartz 		European Journal of Nuclear Medicine 1995
Delayed gastric emptying in patients with liver cirrhosis
H Isobe, H Sakai, M Satoh, S Sakamoto, H Nawata 		Digestive Diseases and Sciences 1994
Stereospecific effects of tryptophan on gastric emptying and hunger in humans
BI Carney, KL Jones, M Horowitz, WM Sun, G Hebbard, MA Edelbroek 		Journal of Gastroenterology and Hepatology 1994
Clinical Efficacy and Prokinetic Effect of the CCK-A Antagonist Loxiglumide in Nonulcer Dyspepsia
AS Chua, M Bekkering, LC Rovati, PW Keeling 		Annals of the New York Academy of Sciences 1994
Satiety and cholecystokinin
KM Pirke, MB Kellner, E Frieß, JC Krieg, MM Fichter 		International Journal of Eating Disorders 1994
Physiological role of cholecystokinin on gastric emptying and acid output in dogs
HO Jin, KY Lee, TM Chang, WY Chey, A Dubois 		Digestive Diseases and Sciences 1994
Effect of Cholecystokinin on Gastric Motility in Humans
C Beglinger 		Annals of the New York Academy of Sciences 1994
Cholecystokinin Hyperresponsiveness in Dysmotility-Type Nonulcer Dyspepsia
AS Chua, TG Dinan, LC Rovati, PW Keeling 		Annals of the New York Academy of Sciences 1994
Role of CCK in the Regulation of Dynamic and Tonic Mechanical Response of the Human Gastric Fundus to Lipids
MA Mesquita, DG Thompson, NK Ahluwalia, LE Troncon, M D'amato, LC Rovati 		Annals of the New York Academy of Sciences 1994
Loxiglumide abolishes the effects of intraduodenal oleic acid on gastric motility and emptying in the pig
M Anvari, CH Malbert, M Horowitz, GG Jamieson 		Neurogastroenterology & Motility 1994
Biological actions of cholecystokinin
JN Crawley, RL Corwin 		Peptides 1994
5 Gut hormones in gastric function
KC Lloyd 		Baillière's Clinical Endocrinology and Metabolism 1994
Role of Cholecystokinin in the Control of Gastric Emptying and Secretory Response to a Fatty Meal in Normal Subjects and Duodenal Ulcer Patients
JW Konturek, P Thor, M Maczka, R Stoll, W Domschke, SJ Konturek 		Scandinavian Journal of Gastroenterology 1994
EJB Reviews 1993
P Christen, E Hofmann 		1994
Physiological role of cholecystokinin on gastric emptying and acid output in dogs
, KY Lee, , WY Chey, A Dubois 		Digestive Diseases and Sciences 1994
The peripheral cholecystokinin receptors
S SILVENTE-POIROT, M DUFRESNE, N VAYSSE, D FOURMY 		European Journal of Biochemistry 1993
Effect of CCK and its antagonists on gastric emptying
C Scarpignato, G Varga, C Corradi 		Journal of Physiology-Paris 1993
Effects of cholecystokinin and gastrin on gastroduodenal motility and coordination in chickens
V Martínez, M Jiménez, E Goñalons, P Vergara 		Life Sciences 1993
Role of Cholecystokinin in the Control of Gastric Acid Secretion and Gastrin Release in Dogs and Healthy and Duodenal Ulcer Subjects
JW Konturek, SJ Konturek, W Domschke 		Scandinavian Journal of Gastroenterology 1993
Role of endogenous bile on basal and postprandial CCK release in humans
M Koide, Y Okabayashi, M Otsuki 		Digestive Diseases and Sciences 1993
Reduced postprandial blood glucose levels in recently diagnosed non-insulin-dependent diabetics secondary to pharmacologically induced delayed gastric emptying
WT Phillips, JG Schwartz, CA McMahan 		Digestive Diseases and Sciences 1993
Cholecystokinin octapeptide stimulates phasic and tonic pyloric motility in healthy humans
R Fraser, D Fone, M Horowitz, J Dent 		Gut 1993
Duration and potency of anticholecystokinin action of subcutaneous and oral loxiglumide on cerulein-stimulated pancreatic exocrine secretion
N Watanabe, M Otsuki 		International Journal of Gastrointestinal Cancer 1993
Gut hormones and diabetes mellitus
W Creutzfeldt, M Nauck 		Diabetes / Metabolism Reviews 1992
Stimulation of pyloric contractions by intraduodenal triglyceride is persistent and sensitive to atropine
R Fraser, D Fone, R Heddle, M Horowitz, J Dent 		Journal of Gastroenterology and Hepatology 1992
Determination of plasma cholecystokinin (CCK) concentrations by bioassay and radioimmunoassay in man. A critical evaluation
M Höcker, WE Schmidt, W Creutzfeldt, AR Choudhury, R Nustede, A Schafmayer, UR Fölsch 		Regulatory Peptides 1992
Relationship of satiety to postprandial glycaemic, insulin and cholecystokinin responses
S Holt, J Brand, C Soveny, J Hansky 		Appetite 1992
VIP inhibits CCK-induced gallbladder contraction involving a β-adrenoceptor mediated pathway in the rainbow trout, Oncorhynchus mykiss, in vivo
G Aldman, S Holmgren 		General and Comparative Endocrinology 1992
Cholecystokinin, gastrin and stress hormone responses in marathon runners
E Philipp, T Wilckens, E Friess, P Platte, K M Pirke 		Peptides 1992
Cholecystokinin receptor antagonist MK-329 blocks intestinal fat-induced inhibition of meal-stimulated gastric acid secretion
KC Lloyd, V Maxwell, TO Kovacs, J Miller, JH Walsh 		Gastroenterology 1992
Cholecystokinin's role in regulation of colonic motility in health and in irritable bowel syndrome
C Niederau, S Faber, M Karaus 		Gastroenterology 1992
The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans
P Cantor, PE Mortensen, J Myhre, I Gjorup, H Worning, E Stahl, TT Survill 		Gastroenterology 1992
Störungen der Motilität des oberen Gastrointestinaltraktes
H Goebell, P Layer 		1992
Influence of various nutrients and their mode of application on plasma cholecystokinin (CCK) bioactivity
J Mssner, M Grumann, J Zeeh, W Fischbach 		The Clinical Investigator 1992
Physiological role of cholecystokinin on postprandial insulin secretion and gastric meal emptying in man. Studies with the cholecystokinin receptor antagonist loxiglumide
M Fried, W Schwizer, C Beglinger, U Keller, JB Jansen, CB Lamers 		Diabetologia 1991
Disturbed cholecystokinin secretion in patients with eating disorders
E Philipp, KM Pirke, MB Kellner, JC Krieg 		Life Sciences 1991
Disordered gastric emptying: mechanical basis, assessment and treatment
M Horowitz, J Dent 		Bailliere's Clinical Gastroenterology 1991
Role of cholecystokinin in the regulation of gastric emptying and pancreatic enzyme secretion in humans
M Fried, U Erlacher, W Schwizer, C Löchner, J Koerfer, C Beglinger, JB Jansen, CB Lamers, F Harder, A Bischof-Delaloye, GA Stalder, L Rovati 		Gastroenterology 1991
Cholecystokinin Antagonists in Gastroenterology
G Adler, C Beglinger 		1991
Sensory Nerves and Neuropeptides in Gastroenterology
M Costa, C Surrenti, S Gorini, CA Maggi, A Meli 		1991
Gastrointestinal adaptation to diets of differing fat composition in human volunteers
KM Cunningham, J Daly, M Horowitz, NW Read 		Gut 1991
Sensory Nerves and Neuropeptides in Gastroenterology: From Basic Science to Clinical Perspectives
M Costa, C Surrenti, S Gorini, CA Maggi, A Meli 		1991
Slow gastric emptying induced by high fat content of meal accelerated by cisapride administered rectally
G Stacher, GV Granser, H Bergmann, A Kugi, G Stacher-Janotta, J Hbart 		Digestive Diseases and Sciences 1991
Effect of dexfenfluramine on gastric emptying of a mixed solid-liquid meal in obese subjects
M Horowitz, A Maddox, J Wishart, J Vernon-Roberts, B Chatterton, D Shearman 		British Journal of Nutrition 1990
Effects of multiple dose infections with Ascaris suum on blood gastrointestinal hormone levels in pigs
S Yang, SM Gaafar, GD Bottoms 		Veterinary Parasitology 1990
Cholecystokinin binding and degradation by isolated rat liver cells
MM Wolfe, M Bougoulias, JE McGuigan 		Regulatory Peptides 1990
Cholecystokinin is not a major hormonal regulator of lower esophageal sphincter pressure
SR Brazer, DS Borislow, RA Liddle 		Gastroenterology 1990
Insulin
P Cuatrecasas, S Jacobs 		Insulin 1990
Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying
E Corazziari, R Ricci, D Biliotti, I Bontempo, AD Medici, N Pallotta, A Torsoli 		Digestive Diseases and Sciences 1990
Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK
RA Liddle, BJ Gertz, S Kanayama, L Beccaria, LD Coker, TA Turnbull, ET Morita 		Journal of Clinical Investigation 1989
ROLE OF CHOLECYSTOKININ IN REGULATION OF GASTROINTESTINAL MOTOR FUNCTIONS
BM Meyer, C Beglinger, JB Jansen, LC Rovati, BA Werth, P Hildebrand, D Zach, GA Stalder 		The Lancet 1989
Gastrin is a major mediator of the gastric phase of acid secretion in dogs: Proof by monoclonal antibody neutralization
TO Kovacs, JH Walsh, V Maxwell, HC Wong, T Azuma, E Katt 		Gastroenterology 1989
Effects of loxiglumide on gallbladder emptying in healthy volunteers
C Niederau, T Heintges, L Rovati, G Strohmeyer 		Gastroenterology 1989
Integrated Actions of Cholecystokinin on the Gastrointestinal Tract: Use of the Cholecystokinin Bioassay
RA Liddle 		Gastroenterology Clinics of North America 1989
Gastrointestinal Peptides
DW Green, G Gomez, GH Greeley 		Gastroenterology Clinics of North America 1989
The rôle of the gastrointestinal tract in the control of voluntary food intake
DV Rayner, PC Gregory 		BSAP Occasional Publication 1989
Physiological role for cholecystokinin in reducing postprandial hyperglycemia in humans
RA Liddle, RJ Rushakoff, ET Morita, L Beccaria, JD Carter, ID Goldfine 		Journal of Clinical Investigation 1988
Cholecystokinin is a physiological hormonal mediator of fat-induced inhibition of gastric emptying in man
JH Kleibeuker, H Beekhuis, JB Jansen, DA Piers, CB Lamers 		European Journal of Clinical Investigation 1988
Proglumide antagonizes cholecystokinin effects on plasma glucose and insulin in rats in vivo
EJ Verspohl, G wunderle, HP Ammon 		European Journal of Pharmacology 1988
Mechanism of actions of cholecystokinin octapeptide on food intake and insulin and pancreatic polypeptide release in the dog
A Inui, M Okita, T Inoue, N Sakatani, M Oya, H Morioka, T Ogawa, N Mizuno, S Baba 		Peptides 1988
Retardation of gastric emptying of solid food by secretin
JH Kleibeuker, H Beekhuis, DA Piers, OB de Muckadell 		Gastroenterology 1988
Somatostatin may not be a hormonal messenger of fat-induced inhibition of gastric functions
MH Mogard, V Maxwell, H Wong, TJ Reedy, B Sytnik, JH Walsh 		Gastroenterology 1988
Advances in Metabolic Disorders
G Aurbach, JT Potts 		Advances in Metabolic Disorders 1964

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