Augmentation of mucosal adaptation following massive small-bowel resection by 16,16-dimethyl-prostaglandin E2 in the rat

Survival following massive resection of the small intestine is often possible due to substantial hyperplasia of the mucosal surface in the remaining small intestine. While nutrients provide the major stimulus for hyperplasia in the clinical setting, the availability of drugs to augment this process would have obvious therapeutic implications. We evaluated the ability of 16,16-dimethyl-prostaglandin E2 (PGE2 to augment mucosal hyperplasia following massive small bowel resection in the rat. Three groups of 7 Sprague-Dawley rats, 160 g body weight, were subjected to 70% jejunoileal resection. One group was given 150 micrograms/kg of 16,16-dimethyl-PGE2 intragastrically twice daily, a second group 75 micrograms/kg subcutaneously, and a third group was untreated. After 17 days, segmental evaluation of mucosal mass in the remaining small intestine was determined by measuring mucosal protein, DNA, and disaccharidase levels. A significantly greater increase in mucosal mass was developed in the duodenum proximal to the anastomosis in both treatment groups, but neither the proximal nor distal ileum demonstrated significantly more adaptation. Histological examination in the duodenum confirmed the presence of a greater adaptive response in both the intragastrically and subcutaneously treated animals. 16,16-dimethyl-PGE2 appears to augment mucosal adaptation following massive small bowel resection in the rat, primarily in the very proximal small intestine.     

Glucose transport by rat small intestine after extensive small-bowel resection

In rats 50 cm of proximal or distal small intestine were resected, preserving duodenum and terminal ileum. Glucose transport was studied 5–6 weeks later, using everted gut sacs from duodenum, ileum, and also from a midgut segment consisting of intestine located preresection at mid-small intestine. Sham-operated animals served as controls: The inner (serosal) fluid medium in sacs from duodenum and midgut gained glucose; ileal sac serosal medium lost glucose. Proximal resection resulted in significant growth of duodenal and midgut mucosa. Duodenal transport specific activity (transport per gram dry mucosa) decreased from control values, but mucosal growth compensated so sac transport capacity (transport per centimeter sac length) remained unchanged. Midgut transport specific activity remained unchanged, thus sac transport capacity directly mirrored increased mucosal mass. Ileal sac serosal medium now accumulated glucose; there was no mucosal growth. Transport specific activity and sac transport capacity of ileum increased in parallel. After distal resection there was no alteration of either duodenal and midgut mucosal masses or transport specific activities, hence sac transport capacities remained unchanged. Ileal sac serosal medium also accumulated glucose, but now both transport specific activity and mucosal mass increased. The resultant increased sac transport capacity was identical to that of ileum after proximal resection. In all sacs from control and resected animals uphill [¹⁴C]glucose concentration differences developed between medium and mucosa. Activity of the mucosal uptake process, assessed in terms of a ratio of mucosal intracellular fluid radioactivity to mucosal medium radioactivity, usually mirrored altered transport specific activity. This indicates that the increased undercoats tissue mass that accompanied increased mucosal mass did not critically affect transport. The most striking findings were: (1) decreased duodenal transport specific activity after proximal resection with mucosal growth compensating; and (2) identical adaptations of ileal segment transport capacities after either proximal or distal small-bowel resections, although mechanisms differed. The present study provides a base for further examinations of carrier-mediated hexose transport after extensive loss of small intestine.     

Effect of chyme on mucosal enzyme levels in small intestine of the rat

Partial jejunectomies, gastrojejunostomies (with closed pylorus), and jejunal Thiry-Vella loops were made in order to elucidate the role of chyme in the control of mucosal mass and the activities of alkaline phosphatase, ATPase, and maltase in the small intestine of the rat. After partial jejunectomy, a partially reversible mucosal hyperplasia was seen in the small intestine with the exception of distal ileum. After gastrojejunostomy a similar hyperplasia took place in the jejunum and proximal ileum. In the jejunal Thiry-Vella loops a mucosal atrophy was found in 4 wk. After partial jejunectomy the activity of alkaline phosphatase decreased slowly in 4 wk in the remaining small intestine with the duodenum as an exception. ATPase activity decreased in the duodenum. Maltase activity remained unchanged during 8 postoperative wk. In gastrojejunostomized rats the activity of alkaline phosphatase and ATPase increased slowly during 12 wk in the jejunum aborally from the gastroenterostomy. A slight depression of maltase activity was observed in the operation area and a slight increase of enzyme activity was found in the middle of the small intestine. In jejunal Thiry-Vella loops the activity of alkaline phosphatase decreased, but no change of maltase activity could be observed during 4 wk. Perfusion of a loop with maltose solution did not cause any changes in the activity of alkaline phosphatase or maltase. The results indicate that after a change in chyme passage the adaptation takes place in the small intestine primarily by the change of mucosal mass, and at least some enzyme levels in the mucosal cells are remarkably stable.     

Changes in serum and intestinal diamine oxidase (DAO) activity after proximal enterectomy in rats

To determine whether serum and mucosal DAO activity reflects quantitative changes in the small bowel mucosal mass, we have chosen an experimental model of mucosal hyperplasia which is known to occur in the rat after enterectomy. A 50% proximal enterectomy or a single transection was performed in 20 growing rats weighing 145–160 g. Ten days following surgery, we determined mucosal mass parameters (weight, protein, and DNA content), sucrase activity, and DAO activity in the duodenum (segment A), proximal ileum (segment B), and distal ileum (segment C) of the remaining small intestine. Mucosal hyperplasia was demonstrated by the finding that in each segment, mucosal weight, protein, and DNA content per centimeter of gut length were significantly (P<0.01) higher (+38 to+78%) in the resected group than in transected controls. In segments B and C of resected rats, the changes in DAO activity expressed per gram of mucosa paralleled the changes in mucosal mass, the activity being increased by +69% and +49% (P<0.05) compared to the values recorded in transected controls. Expressed per centimeter of gut length, total DAO activity was also enhanced by +141% in segment B (P<0.05 vs controls) and by +87% in segment C(P>0.01 vs controls) of resected rats. In the duodenum, the changes in DAO activity were small (+36%) and not significant. In the ileum (segment C), significant correlations were established between total DAO activity and either mucosal weight (r=0.75,N=20,P<0.01) or mucosal DNA concentration (r=0.78, N=20, P<0.01) per centimeter of gut length, but there was no correlation between DAO activity and sucrase activity. Compared to control rats with transection, proximal enterectomy produced marked changes in the serum activity of DAO. Ten days following surgery, the mean value of serum DAO was fivefold higher (P< it0.005) in the resected group than in the transected group. These data indicate that after jejunectomy (1) the intestinal activity of DAO reflects accurately quantitative changes of the mucosal mass in the remaining ileum but not in the duodenum, and (2) circulating levels of DAO could be used as a marker of ileal mucosal adaptation after proximal enterectomy.     

Effect of small bowel resection on the intestinal surface acid microclimate in the rat

The effect of extensive (65%) proximal and middle small bowel resection on the intestinal surface acid microclimate (ISAM) of the remaining ileum in the rat was examined and the results were compared to those of sham-operated rats. ISAM pH measurements were performed in vivo using a pH microelectrode; incubation was performed in Krebs-Ringer phosphate buffer (pH 7.40 +/- 0.02). In the resected rats, ISAM pH of 6.03 +/- 0.07 and 7.22 +/- 0.03 were recorded in the proximal and distal part of the remaining ileum, respectively. In the sham-operated rats, ISAM pH of 6.04 +/- 0.07, 6.98 +/- 0.03 and 7.28 +/- 0.02 were recorded in the proximal jejunum and in the proximal and distal part of the corresponding ileal segment. ISAM pH was significantly lower (p less than 0.01) in the proximal part of the remaining ileum of the resected rats as compared to the corresponding part in the sham-operated rats but was similar in distal ileum. In fact, the ISAM pH of the proximal part of the remaining ileum of resected rats was as acidic as that of the jejunum of the sham-operated rats. These results clearly demonstrate that adaptation in the ISAM occurs in the remaining ileum following extensive resection of proximal and middle small intestine.     

Pyrimidine biosynthetic enzymes in rat intestine after small bowel resection.

After small bowel resection in the rat, mucosal hyperplasia and an increase in nucleic acid synthesis and cell proliferation occur in remaining small intestine. Male Sprague-Dawley rate underwent resection of 50 cm of proximal or distal intestine or sham operation. One month and 6 months after surgery, aspartate transcarbamylase, dihydroorotase, and uridine kinase were assayed in whole mucosa, and in some instances, in crypt mucosa ffrom the remaining intestinal segment. In control bowel, enzyme activity was significantly greater proximal compared with distal segments. One month after proximal or distal resection, mucosal enzyme activity per cm of gut was greater in the remnant bowel compared with controls. There was no such difference at 6 months. Specific enzyme activity of whole mucosa did not increase after resection because the assay was influenced by the disproportionately large contribution of villous protein. Specific enzyme activity (including thymidine kinase) of isolated crypt mucosa was significantly increased 1 month after distal resection. In addition, [3H]thymidine uptake into DNA of crypt mucosa from proximal remnants was also significantly increased. These results indicate that after small bowel resection, the enzymes of pryimidine biosynthesis increase in remaining bowel and parallel the accelerated rate of cell proliferation.     

Zinc absorption following massive small-bowel resection in the rat

Zinc absorption was evaluated six weeks after massive small-bowel resection in rats. Forty rats were divided into four groups. Ten were subjected to proximal small-bowel resection, 10 to distal resection, and 20 served as pair-fed controls. Intestinal perfusion studies were performed using a recirculation technique. Twenty ml of a solution containing 10 g/ml of zinc as zinc sulfate, isotonic sodium chloride, and polyethylene glycol 5 g/liter was perfused for 2 hr through 10 cm of remaining bowel in resected animals and comparable segments in control animals. Zinc uptake was determined and expressed per 0.1 g mucosal dry weight. In control animals, zinc absorption was greatest in the ileum. Animals undergoing distal bowel resection had a compensatory increase in zinc absorption in the proximal small intestine. However, animals undergoing proximal resection did not demonstrate an increase in zinc absorption in the distal bowel. The proximal small intestine appears capable of increasing its capacity for zinc absorption in the response to distal small-bowel resection.     

Neurotensin-like immunoreactivity after intestinal resection in the rat.

Neurotensin is a tridecapeptide located mainly in the distal small intestine. The present study was carried out in order to investigate the neurotensin response after proximal small intestinal resection in the rat. After resection, the median plasma concentration of neurotensin like immunoreactivity (NTLI) was unchanged compared with sham operated rats. Intragastric instillation of fat increased the plasma concentration of NTLI from 45 pmol/l (34-63) in sham operated rats to 92 pmol/l (46-121) in resected rats. No significant increase in the plasma concentration of NTLI was found after intragastric instillation of amino acids or glucose. The tissue concentration of NTLI increased significantly in the jejunum and ileum after proximal small intestinal resection, while the number of immunoreactive neurotensin cells was unchanged. This study shows that the adaptive responses in the distal small intestine after proximal small intestinal resection also involve the neurotensin producing cells.     

Intestinal regrowth is amplified after jejunal but not ileal resection during tapeworm infection in the rat

The ileum possesses functions required by a healthy individual that are not fully supplanted by the duodenum or jejunum. Evidence suggests that the ileum may also be necessary to maintain an enteric parasite–host interaction. We hypothesized that the ileum is essential to the survival of the lumen-dwelling, rat tapeworm, H. diminuta. Male rats were divided into three groups: those with ileal or jejunal resections and nonresected controls. Half of each rat group was infected with the tapeworm. After jejunal resection, the weight but not length of intestinal remnant (duodenum + ileum) in infected rats returned to that of control, nonresected intestine 29 days after surgery and tapeworm numbers were fully maintained. In contrast, after ileal removal intestinal length and weight of the remaining duodenum and jejunum in infected rats were significantly decreased and tapeworm survival diminished. Data indicates that intestinal growth following resection is amplified by tapeworm infection when the ileum remains but diminished when the ileum is removed. Furthermore, loss of the ileum results in decreased infection intensity and dry weight of the tapeworm.     

Cyclic motor activity and trophicity after jejunal resection and bypass in rats

The aim of the study was to examine the changes in intestinal motility induced by an extensive jejunal resection and bypass in rats using an electromyographic technique. The relationship, if any, between the development of motility and adaptive modifications of intestinal trophicity was also studied. A massive jejunal resection, preserving a 7-cm segment distal to the ligament of Treitz, was performed in one group of animals. In a second group, the jejunum was bypassed as a self-emptying blind loop. Two sham-operated groups underwent transection and reanastomosis on the proximal jejunum or ileum. Electromyographic activity was studied at the 10th and 30th postoperative days by means of electrodes implanted throughout the remaining or bypassed bowel and was expressed by means of the pattern of recurrence of the migrating myoelectric complex (MMC). After a month, the animals were sacrificed. Mucosal and muscular wet weight and protein content (mg/cm) of the intestine were then determined. The results showed that 10 days after the jejunal resection in the fasting state, MMC cycle duration is different in the remaining jejunum and in the ileum. However, the distribution of MMC phases in the jejunum was modified and was similar to the one in the ileum. Thirty days after resection, MMC cycle duration, as well as phase distribution in the remaining jejunum, resemble the MMC patterns in the ileum. These changes were not observed after bypass. After the return of MMCs after postprandial inhibition produced by a meal, MMC duration in the ileum was greatly decreased until a month after jejunal resection. In contrast, the jejunal bypass did not produce this modification.     

Factors Affecting Outcome Following Proximal and Distal Intestinal Resection in the Dog (An Examination of the Relative Roles of Mucosal Adaptation, Motility, Luminal Factors, and Enteric Peptides)

In the clinical setting, resection of the ileumresults in an inferior functional outcome compared tojejunal resection. This may be related to a greateradaptive capacity of the ileum, intrinsic structural and functional differences, or regionaldifferences in motor and hormonal function. Our aim wasto evaluate the relative contributions of these factorsto functional outcome after resection of the proximal or distal intestine. Twenty-four dogs underwenteither intestinal transection or 50% resection of theproximal or distal intestine. Studies (nutritionalstatus, absorption, adaptation, motility, peptide levels) were performed every four weeks untilthe animals were killed at 12 weeks. Caloric intake wassimilar in all four groups. Weight loss was greater andmore sustained after distal resection (DR). Serum cholesterol levels decreasedsignificantly only in the DR group. While stool weightand moisture were similar, the DR animals hadpersistent, significant steatorrhea. Intraluminalanaerobic bacteria and SCFA concentrations were significantlygreater in the ileum but were not influenced byresection. Intestinal remnant length increased to agreater extent after proximal resection (PR), butcircumference increased to a similar extent after bothresections. Villus height and crypt depth increasedsignificantly only after PR. MMC frequency was similarin all four groups. In the DR animals 26% of migrating motor complexes (MMCs) originated within theremnant. The jejunal remnant of these animals had adominance of cluster activity similar to the intactdistal ileum. Following PR, the postprandial motilin response was decreased. After DR, there weretransient increases in neurotensin and PYY. Of thevarious factors evaluated, mucosal adaptation and theintestinal motor response appear most likely to explain the inferior nutritional and absorptive outcomeassociated with resection of the distal smallintestine.     

Iron Transport by Rat Small Intestine in Vitro: Effect of Body Iron Status

S ummary . Both mucosal uptake and serosal transfer of iron by everted sacs of rat small intestine were maximal in the duodenum and decreased progressively towards the ileum. Transport of iron against a concentration gradient did not occur in any part of the intestine. When the iron concentration in the bathing medium was varied over the range 10–500 μM a saturable transport process was revealed in the proximal small intestine. In iron-deficient rats mucosal uptake of iron was increased but in iron-loaded rats it remained normal. The results suggest that iron transport across the proximal small intestine of the rat in vitro involves a carrier mechanism which responds adaptively to iron deficiency but not to overload.     

Age related increase of brush border enzyme activities along the small intestine.

Intestinal morphology and brush border hydrolase activities were determined along the small intestine of young adult (three months, n = 10), mature (12 months, n = 10), and senescent (29 months, n = 15) rats. The intestinal segments of the senescent rats contained higher mucosal mass and protein content (p less than 0.05) compared with the young and mature animals. A significant reduction of villus height and crypt depth (p less than 0.05) was found in the proximal intestine during aging. A 35% increase in villus height (p less than 0.05) without changes in crypt depth, was observed in the distal ileum in senescent rats. The activities of sucrase and isomaltase were significantly increased during aging in the duodenum and jejunum (p less than 0.05). Lactase and aminopeptidase activities which showed only minor changes between young and mature animals were significantly enhanced in senescent animals (p less than 0.05) with aminopeptidase exhibiting a three-fold increase in activity in the proximal ileum. The results when combined with those of previous studies suggest that in the aged animal, the increased level of intestinal hydrolase activities may be the consequence of prolonged cellular maturation along the villi in the proximal intestine, and of adaptation to increased concentrations of intraluminal substrates in the distal intestine.     

Induction and maintenance of mucosal enterokinase activity in proximal small intestine by a genetically determined response to mediated sodium transport

Mucosal enterokinase activity was established at intervals throughout the small intestine in guinea-pigs; maximum activity was present in the duodenum and proximal jejunum in new born as well as adult animals. Transposition of 5 cm lengths of small gut from the high enterokinase containing proximal region to the distal intestine and vice versa showed that mucosal enterokinase activity in the transposed segments was little changed after several weeks of healthy life. Isolation of proximal jejunal loops from luminal continuity resulted in the fall of mucosal enterokinase activity to minimal levels within 16 hours. Low levels of mucosal enterokinase activity were identified in loops of both proximal and distal jejunum 12 weeks after isolation. Luminal perfusion studies in vivo in proximal jejunal loops 24 hours after isolation showed that mucosal enterokinase activity could be restored to near normal levels within four to six hours by luminal sodium in the presence of active pancreatic endopeptidases, oligopeptides, L-amino acids, or D-glucose but not D-amino acids or D-fructose. Near normal mucosal enterokinase activity persisted in the loops for as long as luminal perfusion with 144 mM sodium and L-lysine or trypsin was maintained (24 hours). The time course of the restoration of mucosal enterokinase activity was compatible with an initial precursor activation as well as biosynthesis. The requirement for luminal sodium appeared to be absolute regardless of the co-substrate and supports the conclusion that mucosal enterokinase activity is dependent on mediated sodium transport. The ability of proximal intestinal enterocytes to respond to sodium flux with an increase in enterokinase activity is a property determined in intrauterine life: distal intestinal enterocytes may have functioning structural genes for enterokinase but appear to be unable to respond.     

Morphologic and functional adaptations of large bowel after small-bowel resection in the rat

Seventy percent small bowel was resected in rats. Two and four weeks later transport of sodium, chloride, and water was examined in cecum and more distal large bowel (colon) using a well-established in vivo luminal perfusion technique. Sham-operated and unoperated rats served as controls. In cecum mucosa grew 29% by two weeks after resection but transport remained unchanged. There were no further adaptive changes by four weeks after resection. Unexpectedly, cecum of all rats secreted water and electrolytes. The mechanism remains unclear. In colon there were no adaptive changes by two weeks after resection but by four weeks colon mucosa increased 14% and luminal absorption increased proportionately. Separate studies showed hexose transport could not be induced in cecum or colon, although we have previously demonstrated its induction in contiguous remnant ileum.     

Nerve Terminals Containing Neuropeptides Decrease in Number After Massive Proximal Small Bowel Resection in the Piglet

The aim of this study was to evaluate possiblechanges in the neuropeptide innervation pattern of theremaining porcine ileum following 75% proximal resectionof the small intestine. Three-month-old piglets were operated on and two months postoperativelyfullthickness specimens of the proximal part of thedistal ileum wall were taken. Age-matched 3- and5-month-old unoperated piglets were used as controls. The number and intensity of VIP-, galanin-,enkephalin-, substance P-, and somatostatin-containingnerve fibers were estimated in sections processed forimmunofluorescence microscopy and subjected toquantitative scoring. The VIP-, galanin-, andenkephalin-immunoreactive fibers of the circular musclelayer and villi were also quantitated bycomputer-assisted morphometry. The number and intensityof VIP-immunoreactive fibers in the mucosa and circular muscle layermarkedly decreased after resection as compared to3-month-old and 5-month-old controls (P < 0.05). Thegalanin immunoreactivity index decreased significantly after resection in the circular muscle layer ascompared to both control groups (P < 0.05). Theincrease in the number of enkephalin-immunoreactivenerve fibers that normally occurred from 3 to 5 monthsof age was inhibited by the resection. We were notable to see any differences in somatostatin or substanceP immunoreactivity between the groups. The resultssuggest that massive resection induces significant changes in the neuropeptide-containinginnervation of the remaining small intestine. Thesefindings are compatible with altered motor activity andmucosa function in the remain intestine.     

Epidermal growth factor increases intestinal calbindin-D9k and 1,25-dihydroxyvitamin D receptors in neonatal rats

Epidermal growth factor (EGF) has been reported to increase intestinal calcium absorption in suckling rats. The mechanism of this effect is unknown, as are the roles of vitamin D-dependent and independent pathways. The present studies were undertaken to investigate the ability of EGF to accelerate the postnatal induction of the vitamin D-dependent intestinal calcium-binding protein, calbindin-D9k. Subcutaneous administration of EGF increased duodenal calbindin-D9k in suckling rats by more than 100% (P less than 0.001). The effect of EGF was not seen in older weaned animals or when EGF was given to suckling rats by gavage. Administration of EGF simulated the changes of normal development. 1) It increased calbindin-D9k, and the effect was greater in proximal than distal duodenum. 2) EGF increased alkaline phosphatase activity to the same extent in proximal and distal duodenum. 3) EGF increased sucrase more markedly in distal than in proximal epithelium. Maximal and half-maximal effects of EGF on each of these proteins were observed at twice daily doses of 0.1 and 0.04 microgram/g BW, respectively. 4) EGF at the maximally effective dose produced a small (30%) but statistically significant (P less than 0.005) increase in serum 1,25-dihydroxyvitamin D. 5) Most importantly, EGF treatment resulted in a 2-fold increase in intestinal 1,25-dihydroxyvitamin D receptors (VDR) in the proximal segments of the small intestine (P less than 0.001). EGF effects on calbindin-D9k and VDR were specific for the intestine, as EGF did not change kidney calbindin-D9k or kidney VDR. Thus, EGF was able to prematurely initiate a complex series of molecular changes that occur during normal development. The mechanism of EGF's action to stimulate calcium absorption appears to involve a maturation effect on the vitamin D-dependent pathway.     

Intestinal bypass. Bacteriological studies from different parts of the small intestine in rats

Forty-five rats were divided into four groups according to type of operation: 1) end-to-side jejunoileal bypass (ES), 10 rats; 2) end-to-end jejunoileal bypass (EE), 10 rats; 3) jejunoileal resection (R), 10 rats; and 4) no operation, 15 rats. The luminal contents from the proximal jejunum and distal ileum, in groups 1 and 2 also from the proximal and distal part of the excluded small intestine, were examined bacteriologically 5-11 months after operation. The total number of aerobic and anaerobic microbes in the jejunum was equal in all groups. The number of aerobic bacteria in the ileum was significantly higher in the ES group than in the R and U groups. The number of bacteria capable of producing gas in glucose-supplemented media was increased both in the jejunum and ileum after ES bypass. Enterobacteriaceae and Bacteroides were commonly present in the ileum after both types of bypass but were not cultured in jejunal contents. The proximal part of the excluded intestinal segment in groups 1 and 2 contained very low numbers of microbes, whereas the flora of its distal part was similar to that of the ileum in continuity in group 1. Thus, the most marked changes of the intestinal flora occurred after ES bypass in the region of the anastomosis and distal to this.     

The localization of the site(s) of neurotensin release in man and dog

The major source of neurotensin in the gut is the ‘N’ cell and this is found in the highest density in the ileum. The ingestion of food, particularly fat, causes the biphasic release of neurotensin-like immunoreactivity (NTLI) into the circulation. The early peak occurs sooner than expected if it is due to the presence of chyme in the ileum, suggesting that the early release of neurotensin is due to a more proximal concentration of N cells or that neurotensin is released from the ileum by a more proximal stimulus. This paper investigates the site(s) of neurotensin release by studying: three groups of patients with various resections of the small intestine and the fashioning of duodenostomies, jejunostomies and ileostomies; and the dog with chronic gastric, duodenal and ileal fistulae, and following ileal resection. The results indicate that the jejunum and ileum are critical in the release of neurotensin following fat stimulation and that the stomach and duodenum have no direct role. The stimulation of the jejunum by fat causes the early rise of plasma NTLI by releasing neurotensin from the ileum. If chyme is prevented from passing to the distal jejunum the magnitude of the early peak is diminished and the second, later, peak is abolished. The second peak of plasma NTLI is due to the direct luminal stimulation of the distal jejunum and ileum by the products of fat digestion. Ileal resection completely abolishes any release of plasma NTLI in response to fat. It was concluded that the source of neurotensin released by the ingestion of food is the ileum. The release of neurotensin from the distal gut is dependent upon a signal from the proximal to the distal gut. The identity of the signal is unknown, but it is either neural or humoral and previous studies suggest a cholinergic-dependent reflex.     

The ultrastructural bases for coordination of intestinal motility

The electrical control activity (slow waves) of dog small intestine is characterized by phase locking of potential changes in a frequency plateau in the upper intestine. In the distal intestine, phase locking does not occur, though frequencies of each segment are pulled up (increased) by adjacent, more proximal segments. This suggests poorer coupling in the distal compared to the proximal intestine. Electron microscopic studies of the intestine revealed no differences in appearance or number of nexuses (found only in circular muscle) or of intermediate contacts (found in both muscle layers) in duodenum and upper jejunum as compared with ileum. Thus, differences in cell to cell contacts could not explain poorer coupling in the ileum. No difference in innervation of these two regions was observed. However, evidence was obtained that circular muscle cells of the ileum, unlike those of the duodenum, are not oriented perpendicularly to the longitudinal muscle layer. This could provide a structural basis for poorer coupling and for the observed phase lag of potentials around the circumference of the ileum.