Motilin Concentrations Research Articles

Minimal Enteral Feedings Suppress Intestinal Mucosal Growth That Is Not Reversed by Glutamine Supplementation in Neonatal Dogs • 1545

The combination of parenteral nutrition and minimal enteral feedings (MEF), i.e. 10-20% of daily fluid intake, is commonly used in neonates to reduce the risk of necrotizing enterocolitis. We have previously shown that MEF enhances maturation of intestinal motor function but not gut growth in parenterally fed neonatal dogs (Pediatr Res 39:125A). Although glutamine has been shown in some studies to prevent mucosal atrophy, it has not been established whether its addition to MEF can enhance gut growth in healthy gut. Our hypothesis was that MEF+Glutamine would enhance gut growth as well as maturation of motor function. Methods: We placed central venous catheters in 31 newborn puppies from 6 litters who were given 200 ml/kg/d parenterally. Puppies were then randomly assigned to 4 groups: No enteral feeds(NPO), MEF(20 ml/kg/d), MEF+Glutamine and MEF+Glutamate (to control for protein intake). Enteral feeds were comprised of a pooled mixture (1:1) of canine and human milk enriched with either glutamine or glutamate at 0.4g/10 ml (800 mg/kg/d). Pups were gavage fed 5 times daily for 4 days and the volume of parenteral nutrition was reduced in the 3 MEF groups by the volume of enteral feedings given. Fluid intake was adjusted daily for weight gain. After 4 days, motor activity was then recorded for 2 hr and blood samples drawn for motilin and gastrin concentrations. Abdominal organs were then harvested for physical/biochemical assessment of growth. Results: There were no differences among the 4 groups with respect to overall weight gain or weight of stomach, intestine, liver or intestinal length. The DNA content (mg/kg body wt.) in duodenum and the protein contents of the duodenum, jejunum and ileum of the fed groups were all significantly lower compared to those seen in the NPO group(ANOVA/Fishers; all p<0.05). There were no significant differences in plasma gastrin or motilin concentrations. The duration of migrating motor activity was significantly higher in the Glutamine supplemented group compared to the Glutamate or NPO groups but not from MEFgroup. Conclusion: Although enteral glutamine does not augment maturation of motor function beyond that induced by MEF, enteral glutamate appears to suppress it. Minimal enteral feedings with or without glutamine or glutamate supplementation does not cause body or organ weight changes; indeed, MEF decreased mucosal growth. We speculate that enteral feeds may challenge the intestinal mucosa by causing local inflammatory responses which prevents growth.

Effect of leucine 13-motilin (KW5139) on early gastric stasis after pylorus-preserving pancreatoduodenectomy.

To test a hypothesis that exogenously administered motilin would improve early gastric stasis after pylorus-preserving pancreatoduodenectomy (PPPD). Prolonged gastric stasis is a frequent complication after PPPD. We demonstrated that this might at least in part be attributable to delayed recovery of phase III activity of the gastric migrating motor complex due to low concentrations of plasma motilin caused by resection of the duodenum. Ten patients with a mean age of 54 years (range, 33-70) who underwent PPPD were studied. An assembly of manometric tubes was placed in the gastric antrum and jejunum (neoduodenum) at surgery. A gastrostomy tube was added for drainage and volume measurements of the gastric juice. After baseline recording, saline as a placebo was given intravenously on day 14 and 0.5 microg/kg of KW5139 (leucine-13 motilin) was given on days 17 and 18 every 2 hours, 6 times a day. The daily volume of gastric juice output and a gastric motility index were measured. The mean period until the first appearance of phase III activity in the stomach was 41 +/- 2 days. The injection of saline did not change the gastric motility index (7.3 +/- 1.1 to 7.1 +/- 1.3 mmHg; p = 0.72). In contrast, motilin resulted in a significant increase in the gastric motility index (7.5 +/- 1.0 to 17.7 +/- 2.0 mmHg; p < 0.001). The saline injection produced no change in the daily gastric juice output (1175 +/- 140 to 1393 +/- 193 mL; p = 0.09). Motilin significantly decreased the gastric juice output (1387 +/- 157 to 934 +/- 142 mL; p = 0.01). These data indicate that KW5139 is a safe and effective prokinetic drug for the treatment of early gastric stasis after PPPD.

Postsynaptic enhancement by motilin of muscarinic receptor cation currents in duodenal smooth muscle.

We have investigated a potential role of motilin in amplifying the postsynaptic muscarinic responses in the rabbit duodenal smooth muscle cells, using the whole cell variant of patch-clamp technique. Stimulation of motilin receptors by exogenously applied motilin (1 nM) resulted in a large increase in carbachol (CCh)-induced atropine-sensitive cation current (ICCh) at threshold concentrations of CCh (0.3-1 microM) at 30 degrees C. This potentiation was abolished in the presence of a specific blocker of motilin receptor (GM109) and was attenuated with increased concentrations of either motilin or CCh, being virtually absent with maximally effective concentrations of these agonists. Motilin failed to potentiate ICCh when the ambient temperature was reduced to 20 degrees C or if the cation current had been directly activated by internal perfusion with guanosine 5'-O-(3-thiotriphosphate) (50 microM) bypassing the muscarinic receptor. These results suggest that some biochemical processes, such as enzymatic reactions, might be involved in the motilin-induced potentiation and that its site of action might be the muscarinic receptor and/or associated G proteins.

Disturbed initiation of gastric interdigestive migrating complexes despite high plasma motilin levels in patients with low gastric pH.

It is known that there is a close relationshipbetween serum motilin fluctuation and the initiation ofgastric interdigestive migrating complexes (IMC) (1).The administration of synthetic motilin initiates IMC (2), and antimotilin serum blocks theinitiation of IMC (3). Erythromycin has recently beenshown to be a motilin-receptor agonist (4), and motilinreceptors have been found in the human stomach (5). At present motilin is considered to initiateIMC through both the vagal cholinergic pathway anddirect stimulation of smooth muscle. From the clinicalpoint of view, Labo et al (6) and our group (7) recently reported on the relationship between a lowmotilin concentration and disturbance of IMC in patientswith dyspepsia. On the other hand, little is known aboutthe effect of an abnormally high motilin concentration on gastroduodenal motility. We have found threeoutpatients in our clinic at Gunma University Hospitalwith duodenal ulcer or duodenitis who had disturbedinitiation of IMC despite an abnormally high plasma motilin concentration.

Motilin controls cyclic release of insulin through vagal cholinergic muscarinic pathways in fasted dogs.

The effect of motilin on insulin release has not been studied in the interdigestive state. Adult mongrel dogs were chronically implanted with force transducers in the stomach and duodenum to monitor contractile activity, and the plasma motilin and insulin concentrations were measured by a specific radioimmunoassay and enzyme immunoassay, respectively. The concentration of insulin in plasma was found to fluctuate in close association with that of motilin and phase III of the interdigestive migrating contractions in the stomach. This spontaneous release of insulin was mimicked by intravenous infusion of motilin at a dose of 0.3 microgram.kg-1.h-1. Exogenous motilin (0.01-0.3 microgram/kg) dose dependently stimulated insulin release, which was abolished by atropine, hexamethonium, ondansetron, and truncal vagotomy. Phentolamine significantly enhanced, whereas propranolol inhibited, motilin-induced insulin release. In a perifusion system using islet cells from the canine pancreas, motilin did not affect insulin release. In conclusion, motilin stimulates insulin release through vagal cholinergic, muscarinic receptors on pancreatic beta-cells, and the effect appears to be modulated by adrenergic nerves.

Motility of the canine pyloric ring following a pylorus-preserving pancreatoduodenectomy.

Recently, function-preserving operations have become popular, and pylorus-preserving pancreatoduodenectomy (PPPD) is frequently performed for diseases of the head of the pancreas. However, there are only a few basic studies on the pyloric function after PPPD. Using strain gauge force transducers (SGTs), we studied the pyloric motility of normal and PPPD dogs. We prepared three normal and three PPPD dogs in which the SGTs were implanted onto the antrum and pyloric ring, etc. In conscious dogs, the spontaneous gastrointestinal motility was recorded, and the plasma motilin concentration was measured during the interdigestive state. Following the administration of exogenous Leu13-motilin, the motility was again recorded. The relaxation and opening of the pyloric ring was observed synchronously with intense contractions of the antrum during the phase III of normal dogs. Phase III-like motility was recorded in the PPPD dogs, which was not a typical periodic motility. The plasma motilin concentration of one PPPD dog could be measured, and the motilin levels during the phase III-like motility were higher than during phase I. The phase III-like motility was induced by Leu13-motilin in both normal and PPPD dogs. The phase III-like motility recorded in the PPPD dogs was not a typical periodic one, and this aberrant motility was considered to be one of the causes of delayed gastric emptying. Phase III-like motility was induced by the administration of Leu13-motilin; therefore, it is possible that Leu13-motilin improved the motility of the pyloric ring after PPPD.

Actions of the 5-hydroxytryptamine 1 receptor agonist sumatriptan on interdigestive gastrointestinal motility in man

Background—Pharmacological studies of the enteric nervous system have shown the presence of several subtypes of 5-hydroxytryptamine (5HT) receptor, which might be involved in control of the migrating motor complex.Aims—To study...

Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants.

In adults, migrating motor complexes (MMCs) appear to be partially under hormonal modulation by motilin and pancreatic polypeptide. Preterm infants do not exhibit MMCs until 32 wk of gestation. Although plasma concentrations of motilin are similar in infants and adults, it is not known if actual hormonal modulation of MMCs is present in infants. In the first study we assessed whether plasma concentrations of motilin and pancreatic polypeptide surge with the occurrence of MMCs in term infants. In the second study we assessed whether erythromycin, a motilin receptor agonist, could induce migrating motor activity in preterm and term infants. In the first study we recorded motor activity in nine term infants who had never been fed. We determined plasma concentrations of motilin and pancreatic polypeptide in the presence and absence of MMCs. In the second study we gave the motilin agonist erythromycin intragastrically to 21 infants at a range of 24-42 wk of gestation to assess whether migrating activity could be induced via the motilin receptor. In the first study, plasma concentrations of motilin were similar during the presence and absence of MMCs, as were plasma concentrations of pancreatic polypeptide. In the second study, the administration of erythromycin induced the appearance of migrating activity in 7 of 14 infants who were older than 32 wk but in none of the infants who was younger than 32 wk. Although the motilin receptor appears to be functionally present beyond 32 wk of gestation, as assessed by in indirect pharmacologic challenge, hormonal modulation of migrating activity in the neonate by plasma motilin and pancreatic polypeptide is absent.

Effect of nitric oxide synthase inhibition on plasma motilin release in fasted dogs

Inhibition of nitric oxide (NO) synthase on plasma motilin concentrations is not known. The aim of this study was to examine the effect of NO synthesis inhibitor on gastrointestinal motility and motilin release in conscious dogs. Dogs fitted with force transducers were given N ω -nitro-L-arginine (L-NNA) after the termination of phase III contractions. Blood samples were taken for measurement of motilin concentrations. L-NNA induced phase III-like contractions in the stomach and duodenum in association with a significant increase in motilin level. Atropine or hexamethonium significantly inhibited L-NNA-induced phase III-like contractions and the increase in motilin level. Ondansetron markedly inhibited gastric, but not duodenal, phase III-like contractions without affecting the increase in motilin level caused by L-NNA. Vagotomy affected neither the occurrence of phase III-like contractions nor the increase in motilin level produced by L-NNA. We conclude that inhibition of NO synthesis stimulates motilin release via cholinergic pathways independent of the vagus, and induces phase III-like contractions in the stomach and duodenum. Phase III-like contractions induced by L-NNA are mediated through the activation of 5-HT 3 receptors.

Reduced food intake after jejunoileal bypass: a possible association with prolonged gastric emptying and altered gut hormone patterns

The object of this study was to examine whether eating behavior, food preference, gastric emptying, and gut hormone patterns are altered after jejunoileal bypass (JIB) in patients with severe obesity. Eight obese [mean (+/- SD) body mass index (BMI; in kg/m2) 42.9 +/- 4] subjects were studied prospectively before and 9 mo after JIB with eight age- and sex-matched normal-weight control subjects. Total energy intake, data from the universal eating monitor (VIKTOR), eating motivation measured by visual analog scales, a food-preference checklist, a forced-choice list, solid-phase gastric emptying, and postprandial concentrations of cholecystokinin, motilin, and neurotensin were studied. BMI was reduced by 29% after JIB. Compared with normal subjects, the JIB patients showed a reduced desire to eat, decreased hunger, and reduced prospective consumption before a test meal. After surgery, obese subjects selected fewer food items and showed a reduced preference for high-carbohydrate and high-fat items before a test meal. There was a trend from an accelerated toward a decelerated eating pattern in obese subjects after JIB. After JIB, gastric emptying of obese subjects was slowed and similar to that in control subjects. Obese subjects had lower postprandial cholecystokinin concentrations that were lower than those of control subjects both before and after JIB. Postprandial concentrations of neurotensin were higher after JIB. We conclude that after JIB, the desire to eat and preference for high-carbohydrate and high-fat items is reduced, resulting in decreased energy intake. That gastric emptying is prolonged and gut hormone patterns are altered with low postprandial plasma cholecystokinin and high neurotensin plasma concentrations may at least partly account for these observations.

Rhythmic oscillating complexes in gastrointestinal tract of chickens: a role for motilin.

Rhythmic oscillating complex (ROC) is a highly organized gastrointestinal motility pattern recently described in fasted avian species. ROCs show several high-speed aborad-propagated contractions that progressively change into others of orad direction. In addition, chickens show migrating motor complexes (MMC) in both fed and fasting states. Recently, motilin was isolated and characterized from chicken small intestine. Accordingly, the aim of this study was to learn whether chicken motilin might be involved in either ROC or MMC induction. Electromyographic recordings were obtained from different areas of the gastrointestinal tract of chickens while motilin was infused. The response to chicken motilin was dose dependent in both fed and fasted animals; a bolus of 4 x 10(-11) mol/kg (n = 5) did not modify the intestinal motor pattern, whereas 4 x 10(-10) and 4 x 10(-9) mol/kg (n = 5 each) induced a complete ROC pattern of 5.2 +/- 0.6 and 10.8 +/- 0.9 min, respectively. ROCs induced by chicken motilin presented exactly the same pattern as that described during a spontaneous ROC. Furthermore, motilin concentration in plasma, measured by radioimmunoassay, increased during a spontaneous ROC. This study suggests that chicken motilin triggers an ROC in chickens. The fact that plasma motilin levels increased during spontaneous ROC strongly suggests that motilin is involved in the induction of the ROC pattern. Motilin seems to play a different role in avian and mammalian species, because a phase III of the MMC was never induced by motilin infusion.

Meal-induced secretion of gastrointestinal regulatory peptides is not affected by sleep.

The mechanisms responsible for the disruption of the migrating motor complex (MMC) by feeding are not fully understood. Sleep reduces the duration of the postprandial or fed pattern of motility in the intestine. This study was set out to determine if this effect is associated with sleep-induced changes in the secretion of regulatory peptides in response to food. Duodenojejunal motility was studied in 15 healthy ambulant subjects for 2 consecutive days. On one day identical solid meals were consumed in the morning and late in the evening, the latter followed by sleep. On the other day, identical liquid meals were infused into the stomach and the duodenum in the morning and late in the evening, the latter after the onset of sleep. Plasma concentrations of gastrin, neurotensin, peptide YY (PYY), pancreatic polypeptide (PP), motilin and glucose were monitored before and after meals. Sleep significantly shortened the duration of the fed pattern after the solid meal and even more so after the liquid meal. The plasma concentrations of all peptides, except motilin, increased significantly following each meal. Blood glucose levels rose after each meal, the changes being similar with all meals. Food-induced gastrointestinal regulatory peptides secretion and intestinal absorption of glucose are not affected by sleep. The vagal response to a meal, as indicated by PP release, is intact during sleep. The results support the importance of neural mechanisms in the modulation of the postprandial pattern of intestinal motility.

Motilin is a biosignal controlling cyclic release of pancreatic polypeptide via the vagus in fasted dogs.

The mechanism of associated fluctuations in plasma motilin and pancreatic polypeptide (PP) concentrations was studied in fasted conscious dogs while gastric motility was monitored. Plasma motilin and PP concentrations were measured by radioimmunoassay. In intact normal dogs, exogenous motilin (0.03-0.3 g/kg) stimulated dose-related release of PP, but PP did not stimulate motilin release. Motilin-induced PP release was completely inhibited by pretreatment with cholinergic blockers and a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and by vagotomy. The cyclic release of PP was abolished after vagotomy and duodenectomy. However, PP release stimulated by exogenous motilin was apparent after duodenectomy but not after vagotomy. In conclusion, motilin appears to stimulate PP release via vagal, cholinergic muscarinic pathways involving 5-HT3 receptors and to act as a biosignal controlling PP release by mediating the interdigestive periodic changes in the duodenum to the center of the autonomic nervous system. This represents a new role for motilin.

A Double-Blind Placebo-Controlled Study on the Effects of Omeprazole on Gut Hormone Secretion and Gastric Emptying Rate

Background: The present study was designed to investigate whether an effect of omeprazole on gastric emptying is related to changes in the secretion of selected gut hormones. Methods: The studies were performed in healthy men after 10 days' treatment with 40 mg omeprazole daily/placebo. Food ingestion took place in a duodenal phase I, and the meal consisted of an omelette labelled with technetium Tc 99m, followed by 150 ml water labelled with indium In 111. Plasma concentrations of gastrin, cholecystokinin (CCK), and motilin were measured. Results: Pretreatment with omeprazole reduced gastric emptying rates. This applied to all variables and was most pronunced with regard to amounts of solid (median (95% confidence interval)) emptied at 180 min (71% (48-86) for omeprazole versus 96% (87-100) for placebo; P < 0.01). All median values of plasma gastrin concentrations from the omeprazole series were higher than the corresponding values from the placebo series, and omeprazole induced a tenfold increase in incremental integrated area (IIA, pmol/1 × 180 min) of the gastrin concentration curve (5250 (2570-9680) versus 575 (240-1485); P < 0.01). New findings include a lower postprandial secretion of CCK in the omeprazole series and, consequently, a difference in total integrated area (TIA, pmol/1 × 180 min) (88 (21-147) versus 217 (104-267); P < 0.05) and IIA (pmol/1 × 180 min) (52 (2-142) versus 165 (104-195); P < 0.05), respectively; a difference in IIA-30 (pmol/1 × 30 min) of plasma motilin concentrations (270 (140-595) (omeprazole) versus 460 (285-655); P < 0.05); and a direct relationship between the amounts of liquid emptied at 30 min and the corresponding TIA-30 of plasma motilin in the omeprazole (Rs = 0.667; P <0.05) and the placebo series (Rs = 0.767; P <0.05). Conclusion: Pretreatment with 40 mg omeprazole daily decreases the gastric emptying rates and has a substantial influence on the secretion of gastrin, motilin, and CCK. The finding of an omeprazole-induced decrease in CCK release may have clinical implications. Further investigation into the possible effect of proton-pump inhibitors on biliary tract motility and cholesterol solubilization in gallbladder bile is warranted.

Identification of Motilin mRNA in the Brain of Man and Rabbit. Conservation of Polymorphism of the Motilin Gene Across Species

Depoortere, I., P. De Clercq, M. Svoboda, L. Bare and T. L. Peeters. Identification of motlin mRNA in the brain of man and rabbit. Conservation of polymorphism of the motlin gene across species. Peptides 18(10) 1497–1503, 1997.—The data regarding the identity of motilin-like immunoreactivity in the central nervous system are controversial. The aim of the present study was to clarify whether motilin mRNA is present in the brain of rabbit and man. Total RNA, prepared from several regions of the rabbit brain, was subjected to RT-PCR aimed at amplifying a 294 bp cDNA fragment of the rabbit motilin precursor. The amplified product was subcloned and sequenced. The sequence showed 7 differences compared to the one reported for the duodenal precursor [1]. However the duodenal precursor from the rabbit used in the present study revealed identical substitutions. One of these, involving amino acid −11 of the signal peptide, was shown to be due to gene polymorphism, as has also been described at this site in man. By radioimmunoassay the highest concentration of motilin (fmol/mg protein) was detected in the hippocampus (4788 ± 295), the lowest in the telencephalon (2127 ± 221). Using a similar approach, but starting from commercial human brain mRNA, the sequence of a comparable cDNA fragment of the human brain motilin precursor was obtained. Its sequence was identical with the one published for the human intestinal precursor [41]. Our study demonstrates that motilin mRNA is present in the brain of man and rabbit. Together with our recent findings of central motilin receptors, they suggest a central role for motilin.

Muscarinic Control of Phase III Contractions and Motilin Release in Dogs

Yamada, T., A. Mizumoto, M. Satoh, N. Haga and Z. Itoh. Muscarinic control of phase III contractions and motilin release in dogs. Peptides 18 (5) 673–680, 1997.—The role of muscarinic receptor subtype(s) in the control of gastric phase III contractions and motilin release was determined in dogs. Pirenzepine (226 nmol/kg/h) shortened the phase III cycle, causing an early increase in plasma motilin concentrations. Both AF-DX116BS and 4-DAMP inhibited the occurrence of spontaneous and motilin-induced phase III contractions, and 4-DAMP also inhibited the spontaneous increase in plasma motilin concentration. Only 4-DAMP inhibited carbachol-induced motilin release in perifused duodenal mucosal cells. In conclusion, M1 receptors are involved in the indirect inhibition of motilin release. Motilin-induced contractions are mediated mainly by M3 receptors and partly by M2 receptors, and M3 receptors are present in motilin-producing cells.

Exogenous motilin stimulates endogenous release of motilin through cholinergic muscarinic pathways in the dog

BACKGROUND & AIMS: Exogenous motilin is believed to stimulate endogenous release of motilin, but this has not been studied in detail. The aim of this study was to investigate whether and by what mechanism exogenous motilin stimulates endogenous release of motilin in the dog. METHODS: Gastric and duodenal contractile activity in conscious dogs was monitored by chronically implanted force transducers. Plasma canine motilin (c-motilin) concentrations in response to exogenous porcine motilin (p-motilin) were determined by specific radioimmunoassay for c- motilin. The release of motilin from motilin cells obtained from canine duodenal mucosa was studied in vitro using a perifusion system. RESULTS: In vitro, c-motilin release was stimulated by carbachol but not by p-motilin, and the carbachol-induced c-motilin release was inhibited by atropine. In vivo, exogenous p-motilin stimulated endogenous c-motilin release and gastric and duodenal phase III-like contractions; this motilin-induced motilin release was inhibited by atropine, hexamethonium, and a 5-hydroxy-tryptamine 3 receptor antagonist. CONCLUSIONS: In the dog, exogenous motilin stimulates endogenous motilin release through muscarinic receptors on motilin- producing cells via preganglionic pathways involving 5- hydroxytryptamine 3 receptors. (Gastroenterology 1996 Dec;111(6):1456-64)

Pancreatic head resection with and without preservation of the duodenum: Different postoperative gastric motility

Early gastric stasis is a unique complication of pylorus-preserving pancreatoduodenectomy. Because the duodenum proved to be important in the initiation and consolidation of phase III activity of the migrating motor complex of the stomach, the absence of the duodenum and hence gastric phase III may be a cause of gastric stasis. Postoperative gastrointestinal motility was measured with a pneumohydraulic capillary infusion system in nine patients who had undergone pylorus-preserving pancreatoduodenectomy through an indwelling tube assembly placed at operation, and compared with that in six patients who had undergone duodenum-preserving pancreatic head resection. Plasma motilin concentrations were measured by radioimmunoassay. The mean period until the first occurrence of gastric phase III was significantly longer in patients who had undergone a pylorus-preserving pancreatoduodenectomy (40.6 +/- 4.6 days or more) than in patients who had undergone a duodenum-preserving pancreatic head resection (18.8 +/- 4.3 days; p < 0.05). On the day of the first observation of gastric phase III, the plasma concentration of motilin at proximal jejunal phase III in patients who underwent a pylorus-preserving pancreatoduodenectomy (50.2 +/- 9.8 pg/ml) was significantly lower than that at duodenal phase III in patients who underwent a duodenum-preserving pancreatic head resection (184.6 +/- 48.6 pg/ml; p < 0.05). Gastric stasis after a pylorus-preserving pancreatoduodenectomy may be in part attributable to the low concentration of plasma motilin caused by the resection of the duodenum.

Plasma concentration of motilin is changed by antrectomy and selective gastric vagotomy but not cholecystokinin and gallbladder motility

Plasma concentration of motilin is changed by antrectomy and selective gastric vagotomy but not cholecystokinin and gallbladder motility

Time course of adaptive regulatory peptide changes following massive small bowel resection in the dog

Basal and postprandial concentrations of gastrointestinal hormones were measured in 12 dogs before and at one and three months after a 75% small bowel resection. Five animals were studied again at six months. Concentrations of enteric hormones and neuropeptides, measured in the proximal jejunum and distal ileum adjacent to the anastomotic site at the time of euthanasia, were compared with concentrations in control tissues taken from each animal at the time of resection. Increased basal and postprandial levels of gastrin (P < 0.05), cholecystokinin (CCK, P < 0.05), glucose-dependent insulinotropic peptide (GIP, P < 0.01), peptide YY (PYY, P < 0.001), and enteroglucagon (P < 0.001), were seen at one month after small bowel resection. In contrast, no significant changes were seen in concentrations of secretin, motilin, neurotensin, somatostatin, PP, or glucagon. Concentrations of enteroglucagon, GIP, and PYY remained high throughout the six-month study period. In contrast, gastrin and CCK had normalized by three months. Thus, only enteroglucagon, PYY, and GIP showed sustained elevations following enterectomy; the gastrin and CCK changes were transient. Following enterectomy, concentrations of vasoactive intestinal polypeptide (VIP) were reduced by about 50% in mucosal (P < 0.001) and muscle (P < 0.05) layers of proximal and distal gut. In contrast, calcitonin gene-related peptide (CGRP) was increased by about twofold in jejunal and ileal mucosa (P < 0.05), and CGRP elevations were even more marked in the muscle layers (P < 0.001). Somatostatin and neuropeptide Y (NPY) concentrations were similar to controls in all areas except for a small decrease in NPY in ileal mucosa (P < 0.05). These findings suggest that the increased motilin and PP concentrations previously reported after bowel resection in man are more likely to reflect underlying inflammatory bowel disease rather than enterectomy. The normalization of hypergastrinemia explains why the increased acid secretion after small bowel resection is transient. These results provide evidence for independent secretory control of enteroglucagon and PYY, which are both products of intestinal L cells. In addition, these studies reveal marked changes in enteric neuropeptide concentrations following bowel resection. VIP, which is thought to be a major inhibitory transmitter in the gut, is markedly reduced, while CGRP, which is mainly localized in sensory afferent fibers, is increased. These major neuropeptide changes are likely to be of importance in the adaptive responses to massive small bowel resection.