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PubMed1995

2-Naphthalenesulphanyl-L-aspartyl-2-(phenethyl) amide (2-NAP) and food intake in rats: evidence that endogenous peripheral CCK does not play a major role as a satiety factor.

1. The demonstration that systemic administration of the CCKA receptor antagonist, devazepide, increases food intake in rats has provided the strongest support for the hypothesis that endogenous peripherally released cholecystokinin (CCK) acts as a satiety factor. However, interpretation of these results has been confounded by the fact that devazepide can enter the brain from the systemic circulation and may increase food intake by a central action. The present study was therefore undertaken to confirm the hypothesis that endogenous peripheral CCK is a satiety factor by investigating the effects of a novel CCKA receptor antagonist, 2-NAP, which is unlikely to cross the blood brain barrier, on food intake in rats. 2. 2-NAP (1-16 mg kg-1, i.p.) had no significant effects on the intake of a test meal in rats. 3. Pretreatment of rats with 2-NAP (2 mg kg-1, s.c.) abolished the inhibitory effects of exogenous peripheral CCK (5 micrograms kg-1, i.p.) on food intake. 4. In agreement with previous results, devazepide (50-200 micrograms kg-1, i.p.) significantly increased the intake of a test meal in rats. 5. The observations that 2-NAP, which is unlikely to penetrate the blood brain barrier, had no effect on food intake, but that 2-NAP abolished the suppressant effect of exogenous peripheral CCK, suggest that endogenously released peripheral CCK is not important as a satiety factor in rats.

Animals↗
PubMed2005

Selective CCK-A but not CCK-B receptor antagonists inhibit HT-29 cell proliferation: synergism with pharmacological levels of melatonin.

Some data suggest that cholecystokinin (CCK) receptor agonists stimulate the growth of colon cancer. Melatonin, an endogenous indoleamine with strong antioxidant properties, displays antiproliferative and proapoptotic properties both in vivo or in vitro in several types of tumors. We used HT-29 human colon cancer cells, expressing CCK receptors, to test the antiproliferative effects of several antagonists of CCK-A and/or CCK-B and their possible synergism with melatonin. HT-29 cells were cultured in RPMI 1640 medium supplemented with fetal bovine serum at 37 degrees C. Cell proliferation was assessed by the incorporation of [3H]-thymidine into DNA. Annexin V-FITC plus propidium iodine were used for flow cytometry apoptosis/necrosis evaluation. The following drugs were tested: gastrin (CCK-B agonist); CCK-8s (CCK-A agonist); proglumide (CCK-A plus CCK-B antagonist); lorglumide (CCK-A antagonist); PD 135,158 (CCK-B antagonist and weak CCK-A agonist); devazepide or L 364,718 (CCK-A antagonist); L 365,260 (CCK-B antagonist), and melatonin. The results shown a lack of effects of gastrin on HT-29 cell proliferation, whereas CCK-8s induced proliferation at high doses. The order of the antiproliferative effect of the other drugs was devazepide > lorglumide > proglumide. These drugs produce cell death mainly inducing apoptosis. Melatonin showed strong antiproliferative effect at millimolar concentrations, and it induced apoptotic cell death. Melatonin generally enhanced the antiproliferative effects of devazepide, lorglumide and proglumide and increased the proglumide-induced apoptosis. These results suggest that melatonin and CCK-A antagonists are useful for controlling human colon cancer cell growth in culture and in combined therapy significantly increases their efficiency.

Antineoplastic Agents↗
PubMed2002

Cholecystokinin selectively affects presympathetic vasomotor neurons and sympathetic vasomotor outflow.

Cholecystokinin (CCK) is a potential mediator of gastrointestinal vasodilatation during digestion. To determine whether CCK influences sympathetic vasomotor function, we examined the effect of systemic CCK administration on mean arterial blood pressure (MAP), heart rate (HR), lumbar sympathetic nerve discharge (LSND), splanchnic sympathetic nerve discharge (SSND), and the discharge of presympathetic neurons of the rostral ventrolateral medulla (RVLM) in alpha-chloralose-anesthetized rats. CCK (1-8 microg/kg iv) reduced MAP, HR, and SSND and transiently increased LSND. Vagotomy abolished the effects of CCK on MAP and SSND as did the CCK-A receptor antagonist devazepide (0.5 mg/kg iv). The bradycardic effect of CCK was unaltered by vagotomy but abolished by devazepide. CCK increased superior mesenteric arterial conductance but did not alter iliac conductance. CCK inhibited a subpopulation (approximately 49%) of RVLM presympathetic neurons whereas approximately 28% of neurons tested were activated by CCK. The effects of CCK on RVLM neuronal discharge were blocked by devazepide. RVLM neurons inhibited by exogenous CCK acting via CCK-A receptors on vagal afferents may control sympathetic vasomotor outflow to the gastrointestinal tract vasculature.

Animals↗
PubMed2003

Abdominal vagal mediation of the satiety effects of CCK in rats.

CCK type 1 (CCK1) receptor antagonists differing in blood-brain barrier permeability were used to test the hypothesis that satiety is mediated in part by CCK action at CCK1 receptors on vagal sensory nerves innervating the small intestine. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of N alpha-3-quinolinoyl-D-Glu-N,N-dipentylamide, does not. At dark onset, non-food-deprived control rats and rats with subdiaphragmatic vagotomies received a bolus injection of devazepide (2.5 micromol/kg i.v.) or a 3-h infusion of A-70104 (3 micromol.kg(-1).h(-1) i.v.) either alone or coadministered with a 2-h intragastric infusion of peptone (0.75 or 1 g/h). Food intake was determined from continuous computer recordings of changes in food bowl weight. In control rats both antagonists stimulated food intake and attenuated the anorexic response to intragastric infusion of peptone. In contrast, only devazepide was effective in stimulating food intake in vagotomized rats. Thus endogenous CCK appears to act both at CCK1 receptors beyond the blood-brain barrier and by a CCK1 receptor-mediated mechanism involving abdominal vagal nerves to inhibit food intake.

Abdomen↗
PubMed1993

Endogenous cholecystokinin in the control of gastric emptying of liquid nutrient loads in rhesus monkeys.

A role for the brain/gut peptide cholecystokinin (CCK) in the control of gastric emptying has been proposed. In the present studies, we have used a potent type A CCK-receptor antagonist (devazepide) to examine the quantitative contribution of endogenously released CCK in the control of liquid gastric emptying of 100 ml lipid, protein, and carbohydrate test loads in rhesus monkeys. Emptying was studied in conscious monkeys equipped with chronic indwelling gastric cannulas. Prior intragastric administration of devazepide (1.0-320 micrograms/kg) differentially affected the 10-min emptying of glucose (0.125/ml), peptone (4.5%), and Intralipid (4.5%). Glucose emptying was not affected by any dose of the CCK antagonist. The emptying of peptone was accelerated by doses of 10 micrograms/kg or higher. This effect, however, was only partial and plateaued at a dose of 100 micrograms/kg. The gastric emptying of Intralipid was accelerated at a dose of 32 micrograms/kg, and the inhibitory effect of the Intralipid was completely eliminated at a dose of 320 micrograms/kg. At this dose of devazepide, the Intralipid test meal emptied from the stomach at the same rate as physiological saline. These data demonstrate that in rhesus monkeys endogenously released CCK 1) does not play a role in the control of glucose emptying, 2) is a partial mediator of the inhibitory action of peptone on gastric emptying, and 3) is the primary inhibitory mediator in the control of the gastric emptying of Intralipid.

Animals↗
PubMed1993

Blockade of type A, but not type B, CCK receptors postpones satiety in rhesus monkeys.

The exogenous administration of the brain/gut peptide cholecystokinin (CCK) inhibits food intake in a variety of species, including subhuman primates and humans. To determine the role of endogenously released CCK in the control of food intake in rhesus monkeys, we examined the ability of the selective type A and type B CCK antagonists devazepide and L-365260 to affect total daily food intake and various meal patterns. Various doses of the antagonists were administered intragastrically 30 min before a daily 4-h feeding period. One-gram food pellets were delivered in response to lever pulls, and intake was computer monitored. Intragastric administration of the type A CCK receptor antagonist devazepide (10-320 micrograms/kg) significantly increased food intake in a dose-related fashion. The threshold for increasing intake was 32 micrograms/kg, and a maximal effect was obtained at a dose of 100 micrograms/kg that increased total 4-h food intake by 47%. The effect of devazepide on food intake was mediated by significant increases in the size and duration of the initial meal, lengthening of the subsequent intermeal interval, and a decrease in the satiety ratio (intermeal interval/1st meal size). In contrast, intragastric administration of the type B CCK receptor antagonist L-365260 (3.2-320 micrograms/kg) did not significantly affect total food intake or any of the meal parameters. These data demonstrate that endogenously released CCK acting through type A CCK receptors plays a role in regulating food intake in rhesus monkeys.

Animals↗
PubMed1995

Role of cholecystokinin in the anorexia produced by duodenal delivery of oleic acid in rats.

To assess the importance of triglyceride digestion products in producing satiety, we determined the effects of duodenal infusions of triolein, oleic acid, and oleic acid plus monoolein on meal patterns in ad libitum-feeding rats. Oleic acid and oleic acid plus monoolein inhibited feeding similarly; triolein's effect was delayed and fourfold less potent. We then used the type A cholecystokinin (CCK-A)-receptor antagonist devazepide to assess the importance of CCK in mediating the anorexia produced by oleic acid. Oleic acid (at 320, 440, and 640 mumol/h) inhibited 3-h intake dose dependently by 32, 56, and 75%, respectively. Devazepide (1 or 2 mg/kg) blocked the responses to the 320 mumol/h dose, but had little if any effect on responses to the larger doses. Devazepide (1 mg/kg) did block anorexic responses to 3-h cholecystokinin octapeptide infusions (3 and 10 nmol.kg-1.h-1 iv) that inhibited 3-h intake by 25 and 65%, respectively. Our results suggest that the satiety response to triolein is produced by the products of triolein digestion and that CCK plays a significant, indispensable role in mediating the satiety response to duodenal delivery of small but not large loads of oleic acid.

Animals↗
PubMed1999

CCK-A receptor antagonists have selective effects on nutrient-induced food intake suppression in rats.

To provide additional support to the hypothesis that only dietary protein (Pro; chicken egg albumin) and not amino acids (AA; patterned after albumin), carbohydrates (CHO; cornstarch), or fats (Fat; corn oil) produces a satiating effect via CCK receptors, two CCK-A receptor antagonists (PD-140,548 and devazepide) were coadministered with each nutrient. Given alone [4 ml intragastrically (ig)] Pro (1.0 g), AA (1.0 g), CHO (1.4 g), and Fat (2.4 g) suppressed (P < 0.05) food intake on average during the first 2 h of feeding by 1.4 (36%), 1.5 (48%), 1.0 (33%), and 1.2 g (41%), respectively. Devazepide (0.5 mg/kg) and PD-140,548 (1.0 mg/kg) given alone increased food intake during 0-2 h by 0.7 g (18%) and during 0-1 h by 0.5 g (15%), respectively. When coadministered with PD-140,548 (1.0 mg/kg ip), the suppression of food intake caused by Pro was modulated during 0-2 h by 57% (Pro x drug interaction, P < 0.05), but AA-, CHO-, and Fat-induced suppression of feeding was not affected (nutrient x drug interaction, P > 0.05). Devazepide (0.5 mg/kg ip) did not modulate AA-, CHO-, and Fat-induced food intake suppression during any time period (nutrient x drug interaction, P > 0.05). These studies provide additional evidence that CCK-A receptors play a role in Pro (albumin) but not AA-, CHO (cornstarch)-, or Fat (corn oil)-induced food intake suppression in rats.

Amino Acids↗
PubMed1999

CCK-mediated response in the activation of 5-HT receptor types in the guinea-pig ileum.

The possible interaction between cholecystokinin (CCK) and 5-hydroxytryptamine (5-HT) was evaluated in vitro in the longitudinal muscle-myenteric plexus of the guinea-pig ileum. Devazepide and L-365,260 were used to block CCKA and CCK(B) receptors and ondansetron and tropisetron to block 5-HT3 and 5-HT4 receptors, respectively. The CCK receptor antagonists blocked, in a dose-dependent manner, the response to 5-HT and to the selective agonists at 5-HT3 and 5-HT4 receptors, 2-methyl-5-hydroxytryptamine (2-Me-5-HT) and 5-methoxytryptamine (5-MeOT), respectively. The blockade was almost complete on the first phase of the concentration response curve to 5-HT and for all the concentrations of 5-MeOT tested. In the 2-Me-5-HT-induced contractile response there was a component with the same sensitivity to devazepide and to the selective NK1 receptor antagonist, GR 82334, and another resistant component that was abolished by atropine. However, the blockade of the NK1 receptor did not produce a significant increase in the inhibition obtained when atropine or devazepide were separately tested on the 5-MeOT-induced response. These results suggest that CCK is involved in the 5-HT-induced contractile response, particularly in the response induced by 5-HT4 receptor stimulation.

Animals↗
PubMed2000

A cholecystokinin receptor antagonist blocks milk-induced but not maternal-contact-induced decrease of ultrasonic vocalization in rat pups.

The role of cholecystokinin (CCK) in reducing separation-induced ultrasonic vocalization (USV) was examined by peripheral administration (of the selective CCK(A) receptor antagonist devazepide to 10-11-day-old rats. Pups placed alone for 2 min emitted a mean of 55.1 USV/min. When placed on a paper towel wet with warm, sweet milk, USV rate decreased to 23.2/min for the following 8 min. Devazepide (150-600 microg/kg IP) prevented this USV reduction, but did not increase feeding. In contrast, USV reduction produced by contact with the anesthetized dam was not affected by devazepide. Similarly, the opiate antagonist naltrexone (0.5 and 1.0 mg/kg) has been shown to block morphine-induced USV decrease in pups away from the dam, but was ineffective when USV reduction was induced by the presence of the dam (Blass et al., 1990; Carden & Hofer, 1990). The current findings suggest that CCK's role is specific, in that it mediates milk- but not dam-induced quieting of USV. The results, however, are not incompatible with the possibility that CCK and opioids are part of multiple, redundant pathways that mediate the quieting of USV by the dam.

Animals↗
PubMed1993

The benzodiazepine antagonist flumazenil blocks the effects of CCK receptor agonists and antagonists in the elevated plus-maze.

Peripheral administration of the unsulphated cholecystokinin octapeptide (CCK-8us) led to an anxiogenic-like action in the elevated plus-maze model of anxiety in rats. Devazepide and L-365,260 showed potent anxiolytic-like effects at similar doses. The fact that devazepide is 1000 times more potent as a CCK-A receptor antagonist than L-365,260, whereas the two compounds are nearly equipotent at the CCK-B receptor subtype, suggests that CCK-B rather than CCK-A receptors are involved in these effects. Similar results were obtained in mice using the two-compartment test. In the elevated plus-maze, the benzodiazepine antagonist, flumazenil, which was inactive when given alone, significantly antagonized the anxiogenic-like activity of CCK-8us and the anxiolytic-like effects of devazepide and L-365,260. These results suggest a complex interaction between benzodiazepine and CCK receptor mechanisms in the regulation of anxiety states.

Animals↗
PubMed1994

Cholecystokinin and nitric oxide in transient lower esophageal sphincter relaxation to gastric distention in dogs.

BACKGROUND/AIMS: Transient lower esophageal sphincter relaxations have been found to be involved in gastroesophageal reflux. The purpose of this study was to determine whether cholecystokinin (CCK) and nitric oxide are involved in the occurrence of these relaxations. METHODS: Pharyngeal, esophageal, lower esophageal sphincter, and gastric pressures were monitored in five dogs through a cervical esophagostomy. Gastric distentions with air, at a constant pressure of 1.56 kPa, were performed for 30-minute sessions using a barostat. RESULTS: During gastric distention at 1.56 kPa, transient relaxations occurred at a mean rate of 7.2 +/- 0.6 every 30 minutes. CCK-8 infused intravenously (0.1-1 microgram.kg-1.h-1) dose dependently increased the occurrence of relaxations while it was reduced by the CCK-A receptor antagonist devazepide but not the CCK-B antagonist L365260, both administered intravenously in a dose range of 0.1-100 micrograms/kg. The two antagonists administered intracerebroventricularly (1 microgram/kg) did not modify the occurrence of relaxations. Both devazepide and L365260 (10 micrograms/kg) reduced the CCK-induced relaxations, but devazepide was more potent. The nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester (20 mg/kg) reduced the number of relaxations during gastric distention in the presence or absence of CCK infusion. This effect was reversed by L-arginine but not D-arginine (200 mg/kg). CONCLUSIONS: CCK is involved in the occurrence of transient lower esophageal sphincter relaxations through peripheral CCK-A receptors and an L-arginine nitric oxide pathway.

Air↗
PubMed1990

Multiple cholecystokinin (CCK) receptors and CCK-monoamine interactions are instrumental in the control of feeding.

Almost two decades ago, exogenous cholecystokinin (CCK) was shown to suppress food consumption in rats. Since then, CCK has been detected not only in peripheral tissue but extensively throughout the central nervous system. Furthermore, specific CCK receptors have been described, and a distinction drawn between CCK-A and CCK-B receptors. Recently, potent, orally active CCK antagonists, which show a high degree of selectivity for either CCK-A or CCK-B receptors, have been introduced. The present report reviews recent evidence obtained in studies using devazepide (a selective CCK-A receptor antagonist) and L-365,260 (a selective CCK-B/gastrin receptor antagonist). Both compounds increased food consumption and postponed the onset of satiety in well-satiated rats. L-365,260 was more potent, suggesting that central CCK-B type receptors may mediate the satiety effects of endogenously released CCK. Only devazepide was effective in blocking the feeding-suppressant effect of exogenous CCK, indicating that CCK-A type receptors mediate this effect. In a second series of studies, devazepide but not L-365,260 antagonized the anorectic effect of either d-fenfluramine or systemically administered 5-HT. Hence, CCK-A type receptors appear to be involved in the anorectic effects of these serotonergic drugs. We propose that CCK and 5-HT mechanisms involved in mediating satiety are mutually interdependent. Possible interactions between CCK and catecholaminergic mechanisms are also briefly considered.

Animals↗
PubMed1999

Inhibition of gastric emptying by bombesin-like peptides is dependent upon cholecystokinin-A receptor activation.

The amphibian peptide bombesin (BN) and the related mammalian peptides gastrin-releasing peptide (GRP) and neuromedin B (NMB) inhibit gastric emptying in rats. Exogenous administration of BN stimulates the release of cholecystokinin (CCK), a gastrointestinal peptide that also potently inhibits gastric emptying. To determine whether the inhibition of gastric emptying by BN-like peptides is mediated by a CCK-dependent mechanism, we examined the ability of the CCK-A receptor antagonist, devazepide, to block the inhibition of saline gastric emptying produced by BN, GRP18-27 and NMB. Using the same dosages as in the gastric emptying experiment, we also evaluated the effect of devazepide on feeding suppression produced by systemically administered BN. Our results showed that devazepide completely blocked the suppression of gastric emptying produced by BN, GRP18-27 and NMB but had no effect on BN-induced suppression of food intake. These results suggest that BN-like peptides inhibit gastric emptying through an indirect mechanism that is dependent upon CCK-A receptor activation. In contrast, the suppression of food intake by BN, in this experimental paradigm, is independent of CCK-A receptors.

Animals↗
PubMed1995

Profound duodenogastric reflux causes pancreatic growth in rats.

Although duodenogastric reflux is a physiological event, excessive reflux may be a pathogenetic factor in several diseases of the foregut, including cancer. Long term profound duodenogastric reflux produces pancreatic and gastric tumours in rats. The trophic effect of surgically induced duodenogastric reflux on the pancreas was investigated and the mechanisms involved were examined. Rats with profound reflux from a split gastroenterostomy were compared with sham operated and unoperated controls after two and six weeks. In the six week experiment, one reflux and one sham group were given the cholecystokinin (CCK) receptor antagonist devazepide (25 nmol/kg/h). Duodenogastric reflux caused a significant increase in pancreatic weight, DNA, and plasma CCK and gastrin concentrations at both two and six weeks. Devazepide substantially reduced the pancreatic weight increase after six weeks but did not abolish it completely. CCK and gastrin were not affected by devazepide. These results suggest that CCK is largely responsible for the pancreatic growth induced by reflux but another factor may also be involved. The trophic effect of duodenogastric reflux may contribute to the increased incidence of pancreatic cancer reported after gastric surgery.

Animals↗
PubMed1990

Amelioration of cholinergic-induced pancreatitis with a selective cholecystokinin receptor antagonist.

Acute edematous pancreatitis follows excessive cholinergic stimulation in patients exposed to anticholinesterase-containing insecticides. We describe the role of cholecystokinin and the benefits of cholecystokinin receptor blockade in this form of pancreatitis. A cholinergic mimetic (carbachol) was administered to rats weighing 300 to 350 g and produced a form of edematous pancreatitis that mimics that seen in humans. Animals received carbachol intraperitoneally, either alone (250 micrograms/kg of body weight) or with cholecystokinin-receptor antagonist devazepide (3 mg/kg of body weight) and were killed 4 hours later. Carbachol administration resulted in a 19% increase in pancreatic weight, a fourfold increase in serum amylase levels, and a 14-fold increase in serum lipase levels. Plasma cholecystokinin levels, however, were not altered. Devazepide administered prior to cholinergic hyperstimulation blocked pancreatic weight increase and reduced elevations in serum amylase levels twofold and lipase levels fourfold. Although cholecystokinin levels are not elevated in this model of pancreatitis, blockade of even low, background concentrations of this regulatory peptide is beneficial.

Acute Disease↗
PubMed1994

Autocrine growth stimulation of human renal Wilms' tumour G401 cells by a gastrin-like peptide.

The role of gastrin in the control of growth of renal G401 cells isolated from a human nephroblastoma (Wilms' tumour) was investigated. G401 cell growth was enhanced in the presence of exogenous gastrin. Addition of anti-gastrin antibodies to serum-free medium significantly inhibited the growth of G401 cells. G401 cells contained the equivalent of 4.3 pg/10(6) cells of gastrin, and serum-free medium collected over 48 hr from G401 cells contained the equivalent of 38 ng/10(6) cells of gastrin, as determined by radioimmunoassay. Growth of G401 cells was inhibited in a concentration-related way by a variety of gastrin/CCK receptor antagonists. Devazepide and proglumide were, respectively, the most and the least potent inhibitors of G401 cell growth (potency order devazepide > L-365,260 = lorglumide > loxiglumide > benzotript > proglumide). These gastrin/CCK receptor antagonists had similar growth-inhibitory activities in human colonic adenocarcinoma HCT-116 cells. Growth of HCT-116 cells was stimulated to a lesser extent, as compared with G401 cells, by exogenous gastrin, and endogenous gastrin was not detectable in HCT-116 cells. The results are consistent with a role for a gastrin-like peptide in the control of growth of a renal cell line. The data suggest that gastrin/CCK receptor antagonists warrant further investigation as therapeutic agents for the control of gastrin-responsive tumours derived from outside, as well as inside, the gastrointestinal tract, including tumours derived from the kidney.

Benzamides↗
PubMed2002

Serotonin receptor blockade increases food intake and body weight after total gastrectomy in rats.

BACKGROUND: Total gastrectomy often results in early satiety and loss of body weight. Serotonin inhibits food intake, and postprandial serotonin release is increased after total gastrectomy. Serotonin might contribute to early satiety and loss of body weight after total gastrectomy. METHODS AND MATERIALS: Food intake and body weight were investigated with an automated recording system in gastrectomized rats 1-12 months postoperatively. Rats were treated with metergoline, a 5-hydroxytryptamine (5-HT)(1/2) receptor antagonist, two different 5-HT(3) receptor antagonists, a combination of metergoline and devazepide, a cholecystokinin (CCK) a receptor antagonist, or vehicle. In addition, metergoline or vehicle was applied continuously by an intraperitoneal osmotic minipump for 7, 28, or 84 days after total gastrectomy. RESULTS: Metergoline treatment resulted in a dose-dependent increase in food intake in gastrectomized rats. 5-HT(3) receptor antagonist treatment had no effect, and devazepide in addition to metergoline did not further stimulate food intake. Metergoline increased food intake at 1, 3, and 6 months postoperatively by up to 45% (24-h cumulative food intake [FI], 6 months: vehicle 3.83 +/- 0.10, metergoline 5.52 +/- 0.15 g/100 g body weight (BW), P < 0.0001). Chronic metergoline treatment for 7, 28, or 84 days significantly increased food intake after total gastrectomy compared to vehicle treatment (FI 7 days: vehicle 30.83 +/- 0.71, metergoline 36.27 +/- 0.85 g/100 g BW; P < 0.0002; average weekly FI during 28 days; vehicle 31.23 +/- 0.22, metergoline 36.83 +/- 0.33 g/100 g BW, P < 0.0001; average weekly FI during 84 days: vehicle 33.02 +/- 0.59, metergoline 35.07 +/- 0.48 g/100g BW, P < 0.008), and there was a significant body weight increase compared to vehicle treatment (7 days: DeltaBW vehicle -0.7 +/- 1.2 g vs DeltaBW metergoline 9.0 +/- 2.1 g, P < 0.001; 28 days: DeltaBW vehicle 0.3 +/- 2.2 vs DeltaBW metergoline 13.0 +/- 2.3, P < 0.001; 84 days: DeltaBW vehicle 25.7 +/- 10.2 vs DeltaBW metergoline 49.5 +/- 7.2, P < 0.04). Treatment for 84 days resulted in a significant body weight gain, while vehicle treatment had no effect (vehicle: 438 +/- 11 g vs 464 +/- 12 g, P < 0.2, n.s.; metergoline: 448 +/- 9 g vs 498 +/- 10 g, P < 0.007). CONCLUSIONS: Inhibition of food intake by serotonin might contribute to early satiety and loss of body weight after total gastrectomy.

Animals↗