The effect of atropine on bombesin and gastrin releasing peptide stimulated gastrin, pancreatic polypeptide and neurotensin release in man

The effects of 1-h infusions of bombesin and gastrin releasing peptide (GRP) at 50 pmol/kg per h and neurotensin at 100 pmol/kg per h on gastrin, pancreatic polypeptide (PP) and neurotensin release in man were determined following either saline or atropine infusion (20 micrograms/kg). Bombesin produced a rise in plasma neurotensin from 32 +/- 6 to 61 +/- 19 pmol/l and of PP from 26 +/- 8 to 36 +/- 7 pmol/l. There was a further rise of plasma PP to 50 +/- 13 pmol/l after cessation of the infusion. GRP had no significant effect on plasma neurotensin, but compared to bombesin, produced a significantly greater rise in plasma PP from 34 +/- 6 to 66 +/- 19 pmol/l during infusion. There was no post-infusional increase. At this dose, GRP was as effective as bombesin in releasing gastrin, although unlike bombesin its effect was enhanced by atropine. Neurotensin produced a rise in plasma PP from 17 +/- 4 to 38 +/- 8 pmol/l. Atropine blocked the release of PP during GRP and neurotensin infusion. Atropine had no effect on neurotensin or PP release during bombesin infusion, but did block the rise in plasma PP following bombesin infusion. We conclude that, in contrast to meal-stimulated neurotensin release, bombesin-stimulated neurotensin release is cholinergic independent. Despite structural homology, bombesin and GRP at the dose used are dissimilar in man in their actions and sensitivity to cholinergic blockade.     

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.     

Increase of biliary excretion of reverse triiodothyronine in rats during the infusion of neurotensin possibly resulting from the inhibition of iodothyronine 5'-monodeiodination.

Male rats weighing about 350 g were inserted polyethylene tubes into the bile duct and femoral vein under pentobarbital anaesthesia. After taking the first (control) 2-h bile sample the control group (n = 24) was infused saline for 4 h and the other group (n = 14) was infused neurotensin in a dose of 27 micrograms per animal per 4 h. The concentration of thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) in the bile was estimated by radioimmunoassay. No significant differences between groups were found in the biliary excretion of T4 and T3, while the excretion of rT3 after the infusion of neurotensin was significantly increased which was not the case in controls. Since neurotensin is known to increase glycemia which effect might be or might not be mediated by glucagon, it may be suggested that these results bring an additional support for the previously reported coincidence between a prevailing effect of gluconeogenetic hormones and inhibition of iodothyronine 5'-deiodination in the liver.     

Effects of hypo- and hyper-capnia on myocardial blood flow and metabolism during epinephrine infusion in the dog

We have previously demonstrated a 40% increase in myocardial blood flow (MBF) during hypercapnia but no significant decrease of MBF during hypocapnia. The present study was undertaken to evaluate if epinephrine infusion, which increases both myocardial oxygen consumption (MVo2) and myocardial performance, might influence the effects of hypocapnia and hypercapnia on MBF. Induction of hypocapnia was performed by hyperventilation in closed-chest dogs anesthetized with pentobarbital. By adding carbon dioxide to the inspiratory gas, normocapnia and hypercapnia were created. Epinephrine infusion (0.8 microgram X kg-1 X min-1) increased MBF and cardiac output (CO) by 90 and 140%, respectively, while MVo2 was increased by 45%. Epinephrine had a direct coronary vasodilating effect in excess of myocardial needs evidenced by increased oxygen content of the coronary sinus blood. During epinephrine infusion, induction of hypocapnia effected no change of MBF, while myocardial oxygen extraction increased significantly. Although oxygen saturation (So2) and Po2 in the coronary sinus blood decreased, these values remained well above those with hypocapnia without epinephrine infusion, thereby excluding impaired oxygen supply to the heart. Hypercapnia induced an increase of MBF by nearly 40% despite the coronary vasodilatation already induced by epinephrine infusion.     

Effects of plasma norepinephrine elevation on the heart's adaptation to chronic aortic constriction in rats

Chronically elevated plasma norepinephrine has the potential for supporting function of diseased hearts, yet may also initiate harmful biochemical and (or) structural changes in the myocardium. The present study investigated the dosage-related effects of chronic norepinephrine infusion on markers of myocardial damage and then tested the influence of a relatively low norepinephrine infusion rate (0.05 microgram X kg-1 X min-1) on the heart's adaptation to pressure overload in aortic constricted rats. Norepinephrine infusion at 0.50 microgram X kg-1 X min-1 led to significantly increased myocardial hydroxyproline concentration and significant mortality. A rate of 0.25 microgram X kg-1 X min-1 increased myocardial hydroxyproline concentration and mortality in aortic constricted rats but had no such effects on sham-operated rats. The lowest rate tested (0.05 microgram X kg-1 X min-1) significantly increased mean arterial pressure and lung weight of aortic constricted rats, without affecting the degree of left ventricular hypertrophy. This infusion rate and aortic constriction each increased plasma norepinephrine and impaired cardiac performance during rapid preloading, although their combination did not cause further impairment. Thus, it appears that even modest plasma norepinephrine elevation has a negative effect on the heart's adaptation to sustained pressure overload.     

Effects of neurotensin on motor patterns of canine duodenum and proximal jejunum

The aim of this study was to clarify if small doses of neurotensin (2.5 and 5.0 pmol.kg-1.min-1, i.v.) in dogs alter the postprandial motor pattern of the duodenum in comparison with the adjacent jejunum. The intestinal motor patterns were quantified by means of closely spaced strain gauge transducers and a computerized method. An acaloric viscous meal of cellulose was used to induce postprandial motility. Gastric emptying was measured radiographically. During intravenous control infusion of saline, the characteristics of duodenal and jejunal motor pattern were significantly different. The duodenum contracted at a lower rate and showed a higher incidence of stationary contractions. The lower dose (2.5 pmol.kg-1.min-1) of neurotensin showed no significant effects, whereas the higher dose (5 pmol.kg-1.min-1) significantly slowed gastric emptying and altered the motor pattern of both intestinal segments in a similar manner. It reduced the number of contractions, shortened the contraction spread, increased the incidence of stationary contractions, and decreased the incidence of propagated contractions. The alterations of motility caused enhanced mixing of luminal contents. The differences in motor patterns seen in the control state between both intestinal segments were diminished during neurotensin. Data revealed no differences in sensitivity of the duodenum and jejunum to neurotensin. Results suggest that neurotensin is one of the gastrointestinal peptides involved in regulating intestinal contractile patterns.     

Atropine depresses release of neurotensin and its effect on the exocrine pancreas

In this study the effect of 10 and 20 μg · kg^?1 · h^?1 atropine sulfate on release and pancreatic effects of neurotensin was studied in 4 dogs. Neurotensin plasma levels rose significantly when a liquid fat preparation was infused intraduodenally. This rise was almost completely abolished by simultaneous infusion of atropine. Atropine further suppressed basal and fat-stimulated output of pancreatic volume, protein, and bicarbonate; it also reduced pancreatic secretion stimulated by an intravenous infusion of low doses (2.5 to 20 pmol · kg^?1 · min^?1) neurotensin. The effect of higher doses (80 and 240 pmol · kg^?1 · min^?1) of neurotensin was less affected.As neurotensin plasma levels in contrast to normal oral feeding did not rise after sham feeding, our findings suggest that release and action of neurotensin may at least in part be dependent on a cholinergic, non-cephalic mechanism.     

Neurotensin modulates the composition of pancreatic exocrine secretions in chickens

The effects of neurotensin on pancreatic exocrine secretion were examined in fasted, conscious White Leghorn hens. A cannula was surgically implanted in the central duct serving the ventral lobe of the pancreas in order to collect pure pancreatic juice. Following recovery, neurotensin was infused intravenously at 3.6 or 10.8 pmol/kg*min. The volume and pH of the pancreatic secretions were recorded and total pancreatic protein concentration, amylase, lipase, trypsin, and chymotrypsin activity were measured every 30 min for 2 hr and compared to secretions following the infusion of 0.9% saline. Our results demonstrated that neurotensin did not affect the pH nor the pancreatic juice protein concentration, but did increase secretion rate following neurotensin infusion at 3.6 pmol/kg*min. Amylase activity was significantly depressed during neurotensin infusions, while lipase (both pancreatic and carboxylester lipase) activity was significantly elevated. The ratio of amylase to lipase activity was especially depressed by neurotensin infusion at 10.8 pmol/kg*min. Insufficient secretory activity prevented a balanced statistical analysis of chymotrypsin activity, but from a pooled analysis, neurotensin had no effect on protease activity in the pancreatic juice. These results support our current research indicating that neurotensin may be a hormonal regulator of postprandial lipid digestion in chickens.     

Evidence for non-neurotensin receptor-mediated effects of xenin (1-25)--focus on intestinal microcirculation

Xenin (1-25) has been detected in various locations in mammalians. It has structural similarities with neurotensin and its intestinal effects are claimed to be mediated by neurotensin receptors. It has been shown to influence gastrointestinal motility. The effects of xenin (1-25) on intestinal microvascular perfusion after ischemia/reperfusion have not been investigated yet. Therefore, the superior mesenteric artery was clamped for 40 min in Wistar rats (n=8). Ten minutes prior to reperfusion, intravenous infusion of xenin (1-25) (5 nmol/kg/h) was started. By means of intravital microscopy, microvascular perfusion in the mucosal layer was assessed. Animals (n=8) with and without clamping of the superior mesenteric artery and infusion of the carrier solution served as controls.After ischemia/reperfusion, xenin (1-25) increased the density of perfused microvessels and the capillary red blood cell velocity compared to ischemic controls. Capillary red blood cell velocity was elevated (p<0.05). Xenin (1-25) improved the heterogeneous distribution of mucosal blood flow during reperfusion demonstrated by an increase of both the perfusion index and the percentage of perfused microvessels.We conclude that the effects of xenin (1-25) on intestinal microcirculation are significantly different from those previously described for neurotensin. A more complex effector mechanism must be postulated that may involve other regulatory peptides and receptors.     

Exercise, dobutamine, and combined atropine, norepinephrine, and epinephrine compared

We compared the cardiovascular effects evoked in conscious dogs by 1) submaximal exercise; 2) infusion of dobutamine (40 micrograms X kg-1 X min-1); and 3) infusion of a combination of atropine (0.15 mg/kg), norepinephrine (0.19 micrograms X kg-1 X min-1), and epinephrine (0.05 micrograms X kg-1 X min-1). Myocardial O2 demand, as estimated by the double product (heart rate X systolic blood pressure), was similar during all three interventions. Cardiac output and heart rate increased significantly (P less than 0.05) during each of the three interventions. Arteriovenous O2 difference and total body O2 consumption, however, increased only during submaximal exercise. Although myocardial blood flow increased similarly during each of the three interventions, blood flow to skeletal muscle and the tongue increased only during exercise. Exercise and the combined infusion of atropine, norepinephrine, and epinephrine produced similar increases in blood flow to the diaphragm and similar decreases in blood flow to the stomach. These changes in blood flow were associated with appropriate changes in vascular resistance. Additionally, blood flow to the brain, kidney, adrenal glands, liver, and intestine did not change during any of the three interventions. Thus, in dogs, submaximal exercise, infusion of dobutamine, and infusion of a combination of atropine, norepinephrine, and epinephrine to evoke a given level of estimated myocardial O2 consumption produce similar increases in cardiac output, heart rate, and myocardial blood flow. In contrast, the changes in total body O2 consumption, arteriovenous O2 difference, regional blood flow, and regional vascular resistance that occur during each of these three interventions are different.     

Anesthetic dependence of the inhibitory effect of neurotensin on pentagastrin-stimulated acid secretion in rats. A possible role for somatostatin.

The existence of possible local mediators of the inhibitory effect of neurotensin on gastric acid secretion has not been determined. We perfused rats intragastrically with warmed saline and stimulated acid secretion with intravenous pentagastrin, 32 micrograms/kg/hr, and found that anesthesia with pentobarbital resulted in marked inhibition of acid secretion by intravenous neurotensin; however, anesthesia with urethane prevented this inhibitory effect of neurotensin from occurring. In addition, we found a significant increase in somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion in pentobarbital-anesthetized rats. Neither neurotensin nor pentagastrin infusion modified gastric luminal somatostatin-like immunoreactivity after either pentobarbital or urethane, and rats anesthetized with urethane did not show an increase of somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion. These results suggested that somatostatin-like immunoreactivity, released into the portal circulation, was necessary for exogenous neurotensin to inhibit pentagastrin-stimulated gastric acid secretion under these conditions in anesthetized rats.     

High-Affinity Neurotensin Binding Sites in Differentiated Neuroblastoma N1E115 Cells

This paper describes the interaction of neurotensin with mouse neuroblastoma N1E115 cells. Neurotensin binding sites are undetectable in nondifferentiated neuroblastoma cells. They appear during cell differentiation in the presence of a low serum concentration and dimethyl sulfoxide, and reach a maximal level after 50-60 h of incubation under these conditions. The binding of monoiodo[Trp11]neurotensin to homogenates of differentiated N1E115 cells is specific, saturable, and reversible. The interaction is characterized by a dissociation constant of 150 pM and a maximal binding capacity of 9 fmol/mg of protein at 0 degrees C, pH 7.5. These binding parameters, as well as the specificity toward a series of neurotensin analogues, are similar for neurotensin receptors in N1E115 cells and for the high-affinity binding sites that had been previously characterized in rat brain synaptic membranes by means of the same radiolabeled ligand. The presence of high-affinity binding sites for neurotensin in the neuroblastoma N1E115 provides a useful model to study the cellular responses that are generated by the association of neurotensin to its receptor in electrically excitable cells.     

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.     

Mechanisms of excitatory actions of neurotensin on canine small intestinal circular muscle in vivo and in vitro

We have shown previously that close intra-arterial injections of neurotensin in vivo inhibited phasic activity induced by field stimulation of the canine small intestine during anaesthesia but had little effect during quiescence. In contrast, in vitro in the present study, full thickness strips of the muscularis externa cut in the circular axis responded to the lowest effective neurotensin concentrations (10(-12) to 10(-9) M) with an increase in frequency and amplitude of spontaneous contractions; as the concentration was increased from 10(-8) to 10(-7) M, neurotensin inhibited spontaneous activity. A small tonic contraction also occurred; it was maximal at 10(-7) M. Since sufficient tetrodotoxin to block field-stimulated nerve responses did not significantly reduce any of these responses in vitro, the neurotensin responses in vitro did not appear to involve actions on nerves. Indomethacin did not alter the excitatory response to 10(-11) M neurotensin but 5,8,11,14-eicosatetraynoic acid inhibited the excitatory response in a reversible fashion, without altering the response to acetylcholine. Thus excitation in vitro may require the release of excitatory metabolites of arachidonic acid via the lipoxygenase pathway. The neurotensin response in vivo was further studied by evaluating its actions against repetitive submaximal contractions induced by intra-arterial injections of acetylcholine given every minute. Doses that produced a short inhibition of the field-stimulated activity (10(-11) to 10(-10) mol intra-arterially) did not produce inhibition but 10(-10) mol significantly increased the response to acetylcholine. Higher doses (10(-9) mol) produced a significant inhibition of the first subsequent acetylcholine dose but no enhancement of later doses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of arachidonate on permeability and resistance distribution in canine lungs

In this study, 14 canine lung lobes were isolated and perfused with autologous blood at constant pressure (CP) or constant flow (CF). Pulmonary capillary pressure (Pc) was measured via venous occlusion or simultaneous arterial and venous occlusions. Arterial and venous pressures and blood flow were measured concurrently so that total pulmonary vascular resistance (RT) as well as pre- (Ra) and post- (Rv) capillary resistances could be calculated. In both CP and CF perfused lobes, 5-min arachidonic acid (AA) infusions (0.085 +/- 0.005 to 2.80 +/- 0.16 mg X min-1 X 100 g lung-1) increased RT, Rv, and Pc (P less than 0.05 at the highest dose), while Ra was not significantly altered and Ra/Rv fell (P less than 0.05 at the highest AA dose). In five CP-perfused lobes, the effect of AA infusion on the pulmonary capillary filtration coefficient (Kf,C) was also determined. Neither low-dose AA (0.167 +/- 0.033 mg X min-1 X 100 g-1) nor high-dose AA (1.35 +/- 0.39 mg X min-1 X 100 g-1) altered Kf,C from control values (0.19 +/- 0.02 ml X min-1 X cmH2O-1 X 100 g-1). The hemodynamic response to AA was attenuated by prior administration of indomethacin (n = 2). We conclude that AA infusion in blood-perfused canine lung lobes increased RT and Pc by increasing Rv and that microvascular permeability is unaltered by AA infusion.     

The effect of neurotensin and secretin on gastric acid secretion and mucosal blood flow in man

Neurotensin stimulates pancreatic secretion directly and by potentiating the effect of secretin. Neurotensin also inhibits gastric secretion. Secretin inhibits gastric secretion as well, but whether it also interacts with neurotensin is not known. Secretin is known to inhibit gastric mucosal blood flow (GMBF). The effect of neurotensin on GMBF is not known. Acid secretion (triple lumen perfused orogastric tube) and GMBF ([14C]aminopyrine clearance) were therefore measured in 6 subjects during neurotensin, secretin and neurotensin plus secretin infusions. Neurotensin plus secretin reduced acid secretion by a median 130 (range 34-394) mumol/min which was significantly greater than either neurotensin at 36 (7-67) mumol/min or secretin 54 (20-347) mumol/min alone (P less than 0.05). This effect appeared independent of GMBF. Neurotensin plus secretin reduced GMBF by 14 (12-27) ml/min but not significantly more than neurotensin at 11 (3-20) ml/min or secretin 18 (2-27) ml/min alone. Further, there was no correlation between changes in acid output and GMBF during infusion of the peptides. We conclude that the inhibitory effects of neurotensin and secretin on gastric secretion are at least additive and together they may function as an 'enterogastrone'.     

Over-expression of neurotensin high-affinity receptor 1 (NTS1) in relation with its ligand neurotensin (NT) and nuclear beta-catenin in inflammatory bowel disease-related oncogenesis

We investigated the expression of the neurotensin high-affinity receptor 1 (NTS1) during inflammatory bowel disease (IBD)-related colorectal oncogenesis, in colonic samples from 30 patients with IBD-related adenocarcinomas, dysplasias, and inflammatory mucosa (IM). The percentage of NTS1-positive epithelial cells progressively increased from the inflammatory condition to adenocarcinoma and was significantly higher in adenocarcinomas than in IM (p=0.0169). In parallel, the percentage of neurotensin (NT)-positive epithelial cells increased during the IBD-related oncogenesis. Finally, as NTS1 is a ss-catenin inducible gene, we found that a number of preneoplastic lesions and adenocarcinomas co-expressed NTS1 and beta-catenin without NT expression. Therefore, this study suggests two pathways of NTS1 overexpression during IBD-related oncogenesis: one triggered by NT overexpression, and a second associated with an activation of the APC/beta-catenin pathway, these two pathways being not mutually exclusive.     

In-vivo stimulation of rat pancreatic acinar cells by infusion of secretin

Infusion of synthetic secretin in conscious unrestricted rats for periods up to 24 h was used to study the structural and functional adaptation of pancreatic acinar cells to this secretagogue. Initial dose-response studies established 16 clinical units (CU) per kg and h (corresponding to 4.64 micrograms X kg-1 X h-1) as optimal dose for persistent stimulation of enzyme discharge. Infusion of this dose led to a slow but progressive depletion of enzyme stores with minimal content by 12 h stimulation. As a result of persistent stimulation total protein synthesis in the acinar cells increased after a lag period of 3 h and reached maximal values 90% above controls by 6 and 12 h secretin infusion. No structural equivalent for pronounced fluid and bicarbonate secretion was observed for either acinar or duct cells over the entire dose range (1 to 64 CU X kg-1 X h-1) and infusion period (1-24 h), except an increased number of coated vesicles in duct cells. Discharge of enzymes from acinar cells was paralleled by a high frequency of exocytotic images at the luminal plasma membrane and was accompanied by the occurrence of membrane fragments in the luminal space, especially after 3 and 6 h secretin infusion. An increased number of lysosomal bodies at these time points especially in the vicinity of the Golgi complex was interpreted in relation to membrane recycling following massive exocytosis. This pattern of structural and functional adaptation of acinar cells following secretin infusion corresponds to previously described changes following caerulein and carbamylcholine stimulation.     

Effects of intraarterial, intravenous, and intraluminal neurotensin on canine ileal sodium and water absorption and blood flow

Neurotensin is a regulatory peptide which is found primarily in the ileum and is secreted into the blood and lumen. The physiologic effects of neurotensin are uncertain but in certain pathologic states neurotensin increases to levels which can have effects on many organs. The effects of intravenous, intraarterial and intraluminal neurotensin (0.075-7.5 micrograms/min) on fed canine ileal sodium and water fluxes, potassium secretion, and blood flows were studied. Intravenous and intraarterial infusion of neurotensin increased net sodium, potassium, and water secretion, due to increased secretory fluxes, and increased hematocrits. Intraarterial neurotensin was not more effective than intravenous neurotensin except for stimulating potassium secretion. Neurotensin increased potassium secretion at 0.075 micrograms/min IA, increased sodium and water secretion at 0.75 micrograms/min IA and IV, and increased hematocrit at 7.5 micrograms/min IA and and IV. Total and absorptive site blood flows and arterial and venous pressures were not changed. Intraluminal neurotensin had no effects at any infusion rate. Neurotensin can increase potassium secretion at physiologic levels by a local effect and can increase sodium and water secretion at high physiological-pathological levels through a hormonal mechanism. The secretion is not dependent on cardiovascular changes.     

Do normal plasma neurotensin concentrations increase ileal output?

Infusions of neurotensin increase ileal secretion in experimental animals, and the volume of ileal effluent in patients with ileostomies. The aim of the present study was to determine whether normal postprandial plasma concentrations of neurotensin increase the volume of fluid leaving the ileum. Basal and peak postprandial plasma neurotensin concentrations were 23 (17-36) and 39 (25-43) pmol/l (median and range) respectively in five subjects with ileostomies and 15 (3-27) and 32 (15-82) pmol/l respectively in nine normal subjects. Infusion of neurotensin for 30 min at a rate of 6.3 pmol/kg/min into six patients with ileostomies increased ileostomy output about 10-fold, and produced a significant decrease in the concentration of solid material, but plasma neurotensin concentrations rose to 237 (82-422) pmol/l during infusion at this rate. Infusion of neurotensin at 2.3 pmol/kg/min, producing plasma levels of 60 (16-108), had no significant effect the amount or nature of ileostomy effluent. We conclude that normal postprandial plasma concentrations of neurotensin are unlikely to influence the volume of fluid leaving the ileum.