5-Hydroxytryptophan modulates postprandial motor patterns of canine proximal small intestine

The aim of the study was to clarify whether 5-hydroxytryptophan (5-HTP) stimulates the postprandial motor pattern of the duodenum in a similar way as that of the adjacent jejunal segment in dogs. Computerized analysis of motor patterns recorded by closely spaced strain gauges focused on the temporal and spatial distribution of the contractions. Results indicate that 5-HTP increased the incidence and the length of the spread of contraction waves after both an acaloric and a nutrient meal in the duodenum as well as in the adjacent jejunal segment. Effects were more pronounced after the nutrient than after the acaloric meal. After the nutrient meal, but not after the acaloric meal, 5-HTP additionally enhanced the number of both duodenal and jejunal contractions per minute and increased the force of duodenal contractions. The acaloric meal induced significant differences in the motor patterns between the duodenum and the adjacent jejunum. 5-HTP abolished these differences owing to a relatively stronger stimulation of duodenal motility. 5-HTP did not affect gastric emptying of both meals. We conclude (i) that 5-HTP is a potent stimulator of propagated contractions both in the duodenum and the adjacent jejunal segment and (ii) that intestinal motor patterns can be regulated independently of gastric emptying.     

Neuromedin-N inhibits migrating myoelectric complex and induces irregular spiking in the small intestine of rats; comparison with neurotensin.

The effects of neuromedin-N on migrating myoelectric complexes in the small intestine of rats were studied. As neuromedin-N and neurotensin are structurally related peptides a comparison with neurotensin was made. Myoelectric activity was recorded by means of three bipolar electrodes implanted into the wall of the small intestine at 5, 15 and 25 cm distal to the pylorus. The peptides were administered as intravenous infusions to fasted conscious rats. Neuromedin-N at doses of 100-800 pmol kg-1 min-1 caused a dose-dependent disruption of the migrating myoelectric complexes and induced irregular spiking activity (n = 7, P less than 0.05). Neurotensin induced a similar response, but at doses of 1.0-8.0 pmol kg-1 min-1 (n = 5, P less than 0.05). Thus, on a molar basis, neuromedin-N appeared to be about 100-times less potent than neurotensin. Hexamethonium (20 mg kg-1 i.v.) inhibited the migrating motor complexes and induced quiescence, but did not block the effect of neuromedin-N at a dose of 800 pmol kg-1 min-1. Atropine (1 mg kg-1 i.v.) and mepyramine (2 mg kg-1 i.v.) did not affect the migrating motor complexes, nor did they block the effect of neuromedin-N. Simultaneous infusion of neuromedin-N and neurotensin in a 1:1 molar ratio at doses of 2 pmol kg-1 min-1 showed inhibition of the response to neurotensin in eight out of ten experiments. In conclusion, neuromedin-N changes the myoelectric activity in the small intestine from a fasting to a fed pattern.(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatostatin inhibits bombesin-induced effects on migrating myoelectric complexes in the small intestine of the rat

The effect of i.v. infusions of bombesin and somatostatin, administered either separately or in combination, on migrating myoelectric complexes (MMCs) in the small intestine were studied in conscious, fasted rats. The myoelectrical activity was recorded by means of three bipolar electrodes chronically implanted into the duodenum and jejunum. Infusion of bombesin (0.5, 0.9 and 3 pmol . kg-1 . min-1) interrupted the MMC and induced irregular spiking activity similar to that observed on feeding. Only after the highest dose a consistent inhibition of the MMCs and a significant increase (P less than 0.05) of the spiking activity were achieved at all recording levels. Somatostatin (90 pmol . kg-1 . min-1) did not interrupt the MMC, but reduced significantly the incidence of the activity fronts and spiking activity of the MMCs (P less than 0.05). The effects of bombesin (3 pmol . kg-1 . min-1) on the MMC pattern were inhibited by simultaneous infusion of somatostatin (P less than 0.05). In a second series of experiments, using anesthetized rats, infusion of bombesin (0.5 and 3 pmol . kg-1 . min-1) increased the plasma concentration of neurotensin- gastrin-like immunoreactivities in a dose-dependent manner. The results show that bombesin alters the myoelectrical activity of the small intestine from a fasting to a fed pattern. Since the effect of bombesin was inhibited by the hormone release inhibitor somatostatin, it is suggested that the effect of bombesin on MMC may be secondary to the release of gastrointestinal peptides, such as neurotensin or gastrin.     

Role of vagus nerve in postprandial antropyloric coordination in conscious dogs

It is generally believed that gastric emptying of solids is regulated by a coordinated motor pattern between the antrum and pylorus. We studied the role of the vagus nerve in mediating postprandial coordination between the antrum and pylorus. Force transducers were implanted on the serosal surface of the body, antrum, pylorus, and duodenum in seven dogs. Dogs were given either a solid or a liquid meal, and gastroduodenal motility was recorded over 10 h. Gastric emptying was evaluated with radiopaque markers mixed with a solid meal. Dogs were treated with hexamethonium, N(G)-nitro-l-arginine methyl ester (l-NAME), or transient vagal nerve blockade by cooling. A postprandial motility pattern showed three distinct phases: early, intermediate, and late. In the late phase, profound pyloric relaxations predominantly synchronized with giant antral contractions that were defined as postprandial antropyloric coordination. A gastric emptying study revealed that the time at which gastric contents entered into the duodenum occurred concomitantly with antropyloric coordination. Treatment by vagal blockade or hexamethonium significantly reduced postprandial antral contractions and pyloric relaxations of the late phase. l-NAME changed pyloric motor patterns from relaxation dominant to contraction dominant. Solid gastric emptying was significantly attenuated by treatment with hexamethonium, l-NAME, and vagal blockade. Postprandial antropyloric coordination was not seen after feeding a liquid meal. It is concluded that postprandial antropyloric coordination plays an important role to regulate gastric emptying of a solid food. Postprandial antropyloric coordination is regulated by the vagus nerve and nitrergic neurons in conscious dogs.     

Effect of avian neurotensin on motility of chicken (Gallus domesticus) lower gut in vivo and in vitro

Mammalian neurotensin, originally isolated from bovine hypothalamus, differs from avian neurotensin (aNT) by 6 amino acid residues. Bovine neurotensin has been shown to affect motility of chicken crop and rectum and secretion of chicken ileum, but there have been no studies of the effects of aNT on avian intestinal function. This study was designed to characterize the effects of aNT on the motility of the chicken lower gut. Strain gauge transducers were used in vivo to measure contractions of chicken distal ileum, cecum, and distal colon in response to 30-min infusions of aNT at rates of 15, 30, 60 or 600 pmol.kg-1.min-1. In vitro experiments were conducted using segments of distal ileum, cecum or distal colon, stripped of mucosa, cut in either the longitudinal or circular plane, and suspended isometrically in isolated organ tissue baths at a resting tension of 1 g. Avian neurotensin, substance P (SP), or carbamylcholine (CCH) were administered to the bath and the tension generated by each tissue was recorded via a force transducer. A relaxation of chicken ileum was observed in response to aNT infusion in vivo. Except for stimulation of excretation, colon and cecum were not affected by aNT infusion. Both aNT and SP stimulated motility of chicken ileum and cecum in vitro. SP had no consistent effect on colon and aNT only increased contractile force of colon circular muscle. It was concluded that both aNT and SP may have a role in the regulation of lower gut motility in avian species.     

Mechanical factors regulating gastric emptying examined by the effects of exogenous cholecystokinin and secretin on canine gastroduodenal motility

The aim of this study was to elucidate the variables of gastroduodenal motility determining gastric emptying. For this purpose the effects of exogenous cholecystokinin, secretin, and gastric inhibitory polypeptide on motility and gastric emptying were studied during a meal. Motility was measured with extraluminal strain gage force transducers and induction coils in unanaesthetized dogs. The pyloric diameter and the duodenal lumen were evaluated from radiographs. Gastric emptying of an acaloric cellulose meal was determined radiographically. When compared with control infusion of saline, cholecystokinin (1.7 Ivy units X kg-1 X h-1) and secretin (1.7 clinical units X kg-1 X h-1) delayed gastric emptying and diminished the force of the antral contractions, the force and frequency of the duodenal contractions, and opening of the pylorus. The contractile patterns of the duodenum were changed from propulsive to segmenting activity. Cholecystokinin additionally diminished the duodenal lumen. In contrast, gastric inhibitory polypeptide (1.5 microgram X kg-1 X h-1) did not influence gastroduodenal motility and gastric emptying. It is concluded that the motility parameters that were significantly altered by cholecystokinin and secretin are involved in the control of gastric emptying, while other parameters that remained unchanged play a minor role in the regulating process.     

Effects of intracerebroventricular administration of neurotensin,substance P and calcitonin on gastrointestinal motility in normal and vagotomized rats

The effects of intracerebroventricular (ICV) vs. intravenous (IV) injection of neurotensin, substance P and calcitonin on intestinal myoelectrical activity were examined in fed rats. ICV administered neurotensin and calcitonin restored the ‘fasted’ pattern of intestinal activity, i.e. the migrating myoelectric complex (MMC) at a dose as low as 12 and 0.2 pmol, respectively, whereas substance P only reduced significantly ($\text{P < 0.01}$) the duration of the postprandial pattern when injected ICV (48 pmol).Administered systemically at doses 100 times higher than the smallest active doses by the ICV route, calcitonin induced a fasted pattern, while neurotensin and substance P did not modify the fed pattern.The effects of ICV administration of neurotensin and calcitonin were abolished after vagotomy but the shortening effect of substance P on the duration of the postprandial pattern was still present.It is concluded that these three neuropeptides act centrally to control the pattern of intestinal motility in fed rats by shortening the ‘fed’ pattern for substance P and by restoring the MMC pattern for calcitonin and neurotensin, this last effect being mediated by the vagus.     

Regulation of gastric emptying

Studies carried out in the years since William Beaumont's direct observations of gastric motility have provided increased understanding of the physiological roles of the stomach and of the mechanisms for the regulation of gastric motility. Tonic contractions of the proximal stomach are of primary importance for transfer of liquids from the stomach to the duodenum. Peristaltic contractions of the distal stomach are of primary importance for reducing the size of solid food particles and for transfer of solids to the duodenum. Because gastric emptying requires a net antral-duodenal pressure gradient, contractions of the duodenum also influence the rate of gastric emptying. Gastrointestinal hormones, including gastrin, cholecystokinin, secretin, somatostatin, and others, are released by contact of chyme with the intestinal mucosa, and affect contractions of the proximal stomach, distal stomach, and duodenum. Neural reflexes that arise from the stomach act through autonomic motor nerves to allow regulation by the central nervous system of gastric motility. gamma-Aminobutyric acid, opioids, and bombesin may serve as central neurochemical regulators of gastric motility.     

Ghrelin stimulates motility in the small intestine of rats through intrinsic cholinergic neurons

BACKGROUND AND PURPOSE: Ghrelin is a peptide discovered in endocrine cells of the stomach. Since ghrelin mRNA expression and plasma levels are elevated in the fasting state, we investigated the effects of ghrelin on the interdigestive migrating myoelectric complex (MMC) in the small intestine in vivo and compared with motor effects of ghrelin in vitro. Methods: Sprague-Dawley rats were supplied with a venous catheter and bipolar electrodes in the duodenum and jejunum for electromyography of small intestine in awake rats. In organ baths, isometric contractions of segments of rat jejunum were studied. RESULTS: Ghrelin dose-dependently shortened the MMC cycle length at all three recording points. At the duodenal site, the interval shortened from 17.2+/-2.0 to 9.9+/-0.8 min during infusion of ghrelin (1000 pmol kg(-1) min(-1)) and at the jejunal site from 17.5+/-2.2 to 10.5+/-0.8 min. Ghrelin contracted the muscle strips with a pD2 of 7.97+/-0.47. Atropine (10(-6) M) in vitro and (1 mg kg(-1)) in vivo blocked the effect of ghrelin. CONCLUSION: Ghrelin stimulates interdigestive motility through cholinergic neurons. Ghrelin also stimulates motility, in vitro, suggesting that ghrelin receptors are present in the intestinal neuromuscular tissue and mediate its effects via cholinergic mechanisms.     

Involvement of dopamine in the central effect of neurotensin on intestinal motility in rats

The effects of intracerebroventricular (ICV) administration of neurotensin (NT) before a meal on intestinal postprandial motility were examined in conscious rats chronically fitted with intraparietal Nichrome electrodes in the duodeno-jejunum. The effects were compared with those of two analogues, [D-Tyr¹¹]NT and [D-Trp¹¹]NT, resistant to degradation by brain peptidases. NT (10 μg ICV) delayed the occurrence of postprandial disruption of duodenal motility and blocked it on the jejunum. [D-Tyr¹¹]NT and [D-Trp¹¹]NT (1 μg ICV) elicited the same effects but at a ten-fold lower dose. NT administered peripherally just before a meal significantly lengthened the duration of the postprandial motor pattern. The central effect of NT on the fed pattern involved dopaminergic neurons as it was mimicked by dopamine, blocked by haloperidol and partly antagonized by either sulpiride or (+) SCH 23390. It is concluded that: 1) both D₁ and D₂ receptors are involved in the blocking effect of the postprandial disruption induced by central NT; 2) that [D-Tyr¹¹]NT and [D-Trp¹¹]NT are potent agonists at NT receptors in the brain.     

Neurotensin-induced colonic motor responses in dogs: a mediation by prostaglandins

The effects of systemic infusion of neurotensin (NT) were studied in four dogs fitted with strain-gauge transducers implanted on the ascending and descending colon. The motility index of the colon was enhanced for the duration of the 20 min NT infusion (20 pmol X kg-1 X min-1). Such stimulation was comparable to the colonic motor response elicited by feeding, i.e. the gastrocolic reflex. A period of hypomotility, lasting 40-90 min, occurred after either feeding or completion of NT infusion. Pretreatment with prostaglandin synthetase inhibitors, ketoprofene (KTP) and acetylsalicylic acid (ASA), reduced the magnitude of both the NT- and meal-induced hypermotility responses. The results suggest that the ability of NT to increase colonic motility may involve prostaglandin synthesis and that endogenous prostaglandin may exert a physiologic effect on colonic motor response to feeding. Moreover, these findings support a possible role for NT as one of the mediators involved in the non-neural mediation of the gastrocolic reflex.     

Neurotensin increases net fluid secretion and transit rate in the small intestine of man

In a double-blind study with six patients, who previously had undergone proctocolectomy for ulcerative colitis, the ileostomy discharge significantly increased from 110 to 295 ml X 4 h-1 during infusion of neurotensin, 3 pmol X kg-1 X min-1 for 4 h. Transit defined as the passage of a perorally ingested unabsorbable marker (polyethylene glycol, PEG 4000) was significantly increased during the last hour of neurotensin infusion. The dose of neurotensin used in this study has previously been shown to result in plasma levels of neurotensin-like immunoreactivity within the range obtained after a fatty meal. Thus, the present data indicate that neurotensin in man may exert a physiological function by increasing net fluid secretion in the small intestine as well as increasing the intestinal transit rate.     

Neuropeptide Y induces fasted pattern of duodenal motility via Y(2) receptors in conscious fed rats

Neuropeptide Y (NPY), a 36-amino acid peptide abundantly expressed in the brain, has been implicated in the regulation of feeding and visceral functions. The present study was designed to investigate whether or not NPY specifically regulates duodenal motility. The manometric method was used to measure duodenal motility in conscious, freely moving rats. The rat duodenum showed phasic contractions mimicking the migrating motor complex in the fasted state that were replaced by irregular contractions after the ingestion of food. NPY powerfully affected the contractile activity after intracerebroventricular (i.c.v.) administration, changing fed (postprandial) patterns into phasic contractions characterized as fasted (interdigestive) patterns. This effect was mediated via receptors with pharmacological profiles similar to rat Y(2) and Y(4) receptors, although neither Y(1) nor Y(5) agonists had any effects on motility despite potent feeding-stimulatory effects. Immunoneutralization with anti-NPY antiserum administered i.c.v. abolished fasted patterns and induced fed-like motor activities. An i.c.v. dose of peptide YY produced a different effect from NPY, with increase in the motor activities of both fed and fasted patterns. These results indicate that fasted and fed motor activities are regulated processes and that NPY induces fasted activity through Y(2), and possibly Y(4), receptors, which may represent an integrated mechanism linked to the onset of feeding behavior.     

Role of cholecystokinin in postprandial and vagally stimulated duodenal and gallbladder motility in dogs.

This study was designed to determine the role of cholecystokinin (CCK) in postprandial motility pattern of the duodenum and gallbladder (GB) in conscious dogs provided with chronic duodenal electrodes for recording of myoelectric activity and GB fistulas for measurement of intraluminal pressure and volume of GB and to calculate the GB motility index (MI) and GB emptying rate. During naturally occurring activity front (phase III MMC) in the duodenum there was significant increase in the MI of GB accompanied by about 20-30% reduction in the GB volume. These changes in duodenal and GB motility pattern could be duplicated by i.v. motilin. Feeding abolished the appearance of spontaneous activity front in the duodenum and greatly increased motility of GB while reducing its volume. Administration of CCK receptor antagonists in fed dogs failed to affect the motility changes induced by meal in the duodenum but abolished these of the GB. Vagal cholinergic stimulation with insulin, 2DG or urecholine caused similar effects to that induced by food i.e. increased duodenal spike activity, abolished phase III of the MMC, decreased GB volume and increased GB motility. Pretreatment with CCK antagonists did not affect significantly duodenal spike activity or GB motility but significantly increased the GB volume. Atropine 125 micrograms/kg) blocked almost completely spontaneous activity front in the duodenum and accompanying alterations in the motility and volume of GB. We conclude that CCK contributes to the MMC related alterations in the GB motor activity and is essential in cholinergic stimulation induced of the GB emptying but not in vagally induced duodenal and GB motility.     

Action of neurotensin on size, composition, and growth of pancreas and stomach in the rat

Since the gastrointestinal peptide neurotensin has a stimulatory effect on the secretion of the exocrine pancreas and an inhibitory effect on secretion and motility of the stomach, we investigated whether chronic parenteral administration of neurotensin would affect pancreatic and gastric growth. We therefore infused synthetic neurotensin subcutaneously (dose, 43 and 282 pmol X kg-1 X min-1) in 20 Wistar rats for 2 weeks using Alzet osmotic minipumps and compared pancreatic weight, DNA, RNA, protein, lipase, amylase, pancreatic polypeptide and insulin with these parameters in 10 control rats from the same litter with subcutaneously implanted plastic cylinders approximately the size of the minipumps. In another experiment, synthetic neurotensin (836 pmol X kg-1) was injected intraperitoneally three times a day for 3 days in 12 rats. Thereafter, we measured pancreatic DNA and in vitro incorporation of [3H]thymidine into pancreatic DNA. These effects were compared with the actions of caerulein and normal saline. Long term infusion of the high neurotensin dose induced an increase of pancreatic weight (control: 0.87 g, neurotensin: 1.02 g) and of DNA (control: 2.5 micrograms; neurotensin: 3.5 micrograms) and pancreatic polypeptide (control: 2.4 ng; neurotensin: 7.4 ng) contents, whereas pancreatic protein, RNA, amylase and lipase contents were not stimulated. In relation to DNA, these parameters even were significantly depressed. Insulin remained unchanged. Intraperitoneal injection of neurotensin induced an increase of pancreatic DNA content and stimulated [3H]thymidine incorporation into DNA (control: 11 000 dpm/g; neurotensin: 15 800 dpm/g pancreas). Moreover, long-term neurotensin infusion with the high dose led to a rise in protein concentration and an increase in the thickness of the gastric antrum; antral DNA concentration was insignificantly stimulated. Parenteral neurotensin in the doses and at the times administered, led therefore, to hyperplasia of the pancreas and induced growth of the gastric antrum. It is concluded that neurotensin can act as a trophic factor on pancreas and gastric antrum of the rat. It remains to be determined whether this represents a physiological effect of neurotensin.     

Relationship of postprandial motilin, gastrin, and pancreatic polypeptide release to intestinal motility during vagal interruption.

Experiments were performed to determine how postprandial motilin, gastrin, and pancreatic polypeptide plasma concentrations measured during vagal blockade relate to coincident small intestinal motility patterns. Feeding produced a postprandial pattern of intestinal motility coincident with a sustained increase in gastrin and pancreatic polypeptide and a decline in motilin plasma concentrations. Vagal blockade replaced the fed pattern with one similar to migrating motor complex (MMC) activity. Highest motilin plasma concentrations were observed during phase III of this MMC-like activity, as occurs in the fasted state. Vagal blockade reduced but did not abolish the postprandial increase in plasma gastrin and pancreatic polypeptide concentrations. Termination of vagal cooling produced a decline in motilin and an elevation in gastrin and pancreatic polypeptide concentrations, coincident with the return of the fed pattern. In conclusion, during vagal blockade in the fed state (i) motilin, but not gastrin or pancreatic polypeptide plasma concentrations, fluctuate with the MMC-like activity, and any measurement of motilin concentration under these circumstances must be interpreted on the basis of gut motility patterns, and (ii) gastrin and pancreatic polypeptide concentrations are marginally elevated, but these changes are not enough to disrupt the MMC or have any motor effect. Lastly, the fed pattern and the postprandial changes in motilin, gastrin, and pancreatic polypeptide concentrations are in part dependent upon intact vagal pathways.     

Mechanisms underlying nutrient-induced segmentation in isolated guinea pig small intestine

Mechanisms underlying nutrient-induced segmentation within the gut are not well understood. We have shown that decanoic acid and some amino acids induce neurally dependent segmentation in guinea pig small intestine in vitro. This study examined the neural mechanisms underlying segmentation in the circular muscle and whether the timing of segmentation contractions also depends on slow waves. Decanoic acid (1 mM) was infused into the lumen of guinea pig duodenum and jejunum. Video imaging was used to monitor intestinal diameter as a function of both longitudinal position and time. Circular muscle electrical activity was recorded by using suction electrodes. Recordings from sites of segmenting contractions showed they are always associated with excitatory junction potentials leading to action potentials. Recordings from sites oral and anal to segmenting contractions revealed inhibitory junction potentials that were time locked to those contractions. Slow waves were never observed underlying segmenting contractions. In paralyzed preparations, intracellular recording revealed that slow-wave frequency was highly consistent at 19.5 (SD 1.4) cycles per minute (c/min) in duodenum and 16.6 (SD 1.1) c/min in jejunum. By contrast, the frequencies of segmenting contractions varied widely (duodenum: 3.6-28.8 c/min, median 10.8 c/min; jejunum: 3.0-27.0 c/min, median 7.8 c/min) and sometimes exceeded slow-wave frequencies for that region. Thus nutrient-induced segmentation contractions in guinea pig small intestine do not depend on slow-wave activity. Rather they result from a neural circuit producing rhythmic localized activity in excitatory motor neurons, while simultaneously activating surrounding inhibitory motor neurons.     

Motilin and the postprandial motility of the antrum.

This study was designed to establish whether the rise in plasma motilin observed after a meal in humans can influence the postprandial motor activity of the antrum. Antroduodenal postprandial motility profiles and indices obtained from 5 controls and 5 subjects infused with exogenous synthetic motilin (0.1 microgram.kg-1) or with the motilin receptor agonist erythromycin lactobionate (200 mg) were compared. Motilin infusion increased plasma motilin concentrations about 5 times above the physiological range but failed to modify the normal postprandial contractile response. On the other hand, in 4 of the 5 subjects, erythromycin induced an intense motor response that mimicked phase III of the migrating motor complex. Our study demonstrates that, during the postprandial period, motilin antral receptors can be stimulated only with doses of motilin exceeding the physiological plasma concentrations, and that the motor effect obtained did not mimic the usual postprandial motility pattern. Our results, therefore, do not support the proposal that the postprandial motility of the antrum is regulated by the plasma levels of motilin.     

Contribution of neurotensin in the immune and neuroendocrine modulation of normal and abnormal enteric function

Among various hormones, which are synthesized by intestinal cells and influence enteric function, neurotensin (NT) has gained scientific attention the last three decades. This neuropeptide, mainly located in neuronal synaptic vesicles of hypothalamus and in neuroendocrine cells of the small bowel, participates in enteric digestive processes, gut motility and intestinal inflammatory mechanisms by cooperating with other regulators such as histamine, substance P and somatostatin. NT plays an important role mainly in intestinal lipid metabolism by cooperating with cholecystokinin and establishes a hormonal brain-gut-adipose tissue connection, which could adjust appetite, weight status and generally eating behavior with the amount and the content (particularly fat) of food intake. Moreover, NT achieves a multi-level control of intestinal motility by cooperating with the enteric- and central nervous system, and other enteric hormones (such as somatostatin). NT regulates motility patterns related to the efficiency of the digestive process, stool emptying, transition from the fasted to the postprandial state and reestablishment of the fasted status. In addition, NT possesses a long-term enteroprotective role towards the intestinal tract, despite the fact that under certain circumstances NT may participate in short-term subcellular pathways promoting an acute inflammatory response. The aim of this review is two-fold. First, is to provide an up-to-date synopsis of the available knowledge regarding the involvement of neurotensin in enteric functional status, and highlight its significance in physiological and pathological conditions. Second, is to propose new research directions concerning the role of neurotensin and other intestinal regulatory peptides in the establishment of the brain-gut axis and in the development of functional disorders of the abdominal tract. Conclusively, to clarify the areas, in which an experimental therapeutic intervention, based on NT analogs, may lead to encouraging results.     

Variations in plasma motilin, somatostatin, and pancreatic polypeptide concentrations and the interdigestive myoelectric complex in dog

We have looked at the plasma concentrations of motilin, pancreatic polypeptide (PP), and somatostatin (STS) during the various phases of the interdigestive motor complex (IDMC) in dogs. As expected, motilin cyclical increase was always associated with the phase III of the IDMC. Statistical analysis of PP variations revealed a significant rise 10 min before duodenal phase III; however, in individual animals, this relationship was inconsistent. Although a dose-related increase in PP blood levels was induced by administration of synthetic canine motilin (0-200 ng kg-1 iv), fasting plasma levels of PP were not correlated with the concentrations of circulating endogenous motilin. After truncal vagotomy, while motilin release and the intestinal motility pattern remained unaltered, the phase III associated cyclical increases of PP disappeared. Infusion of physiological amounts of PP (1 microgram kg-1 h-1 for 3 h) mimicking the postprandial release failed to reproduce a fed pattern type of intestinal motility and of motilin secretion. No statistical correlation could be established between STS plasma levels and the motor activity of the intestine. STS plasma levels were not correlated with circulating concentrations of motilin and the exogenous administration of physiological doses of synthetic canine motilin failed to modify STS plasma levels. Morphine (200 micrograms kg-1 iv) stimulated only the release of motilin. These data suggest that the role played by circulating concentrations of PP and STS in the control of the IDMC in dog is at most minimal.