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.     

Neuropeptides and thermoregulation: the interactions of bombesin, neurotensin, TRH, somatostatin, naloxone and prostaglandins

In this study we have examined the interactions of bombesin (1 microgram ICV), neurotensin (1 microgram ICV), TRH (10 micrograms ICV), somatostatin (10 micrograms ICV), PGE2 (10 micrograms ICV) and naloxone (10 mg/kg SC) on thermoregulation in the rat at room temperature (20 +/- 1 degree C). Given alone, bombesin, neurotensin, somatostatin and naloxone all produced hypothermia (bombesin greater than neurotensin greater than somatostatin congruent to naloxone). PGE2 was hyperthermic, and TRH had no effect. Bombesin and PGE2 neutralized one another's effects. Neurotensin had no effect on PGE2-induced hyperthermia. Naloxone enhanced the hypothermic effect of bombesin and somatostatin enhanced the rate of onset of hypothermia after bombesin. TRH had no effect on bombesin-induced hypothermia. TRH, somatostatin and naloxone had no effect on neurotensin-induced hypothermia. TRH antagonized the hypothermia due to naloxone and somatostatin.     

Cholinergic responsiveness of intestinal muscle in the pregnant guinea pig

Clinical observations and limited animal experiments have suggested that gastrointestinal motility is suppressed during pregnancy. We therefore compared isometric contractions of colon and ileal circular muscle in response to carbachol (10(-8) to 10(-4) M). Data was analyzed by comparing mean maximal tension, dose-response curves, and EC50 values for tissue from the two groups of animals. Circular muscle from proximal colon, distal colon, and ileum in pregnant animals developed less tension in response to carbachol than did tissue from non-pregnant controls. Dose-response curves in the pregnant groups were depressed, when compared with non-pregnant groups, at concentrations of 10(-6) M and greater. Sensitivity of the muscle to cholinergic stimulation, as measured by EC50 values, was similar in the ileum and proximal colon but increased slightly (p less than 0.05), by a factor of approximately 2, for distal colonic muscle from pregnant animals. Assuming that circular muscle contractions are primarily responsible for mixing and propulsion in the gut, this reduction in responsiveness to excitatory cholinergic stimulation is consistent with the concept of pregnancy-related suppression of gastrointestinal motility.     

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.     

Cholecystokinin stimulates neuronal receptors to produce contraction of the canine colon

The motor effects of cholecystokinin 26-33-amide (CCK octapeptide; CCK-OP) and several purported CCK receptor antagonists on canine colonic circular muscle were determined in pentobarbital anesthetized dogs. Intravenous injections of CCK-OP had no effect on colonic motility at doses that contracted the gallbladder, stomach and duodenum. CCK-OP delivered by intraarterial injection to a small segment of the proximal colon produced a dose related increase in colonic motility with one-half maximum response at 12 ng/Kg and maximum response at 50 ng/Kg. The effects of intraarterial injections of several established CCK-receptor antagonists on proximal colonic responses to intraarterial injections of CCK-OP were determined. Proglumide, 10 mg/Kg, did not produce colonic contractions itself, but antagonized CCK-OP-induced responses. Carbobenzyloxy (CBZ)-CCK27-32-amide antagonized CCK-OP-induced colonic responses and also had no effect on basal colonic motility (0.1-1 and 5 micrograms/Kg). Neither compound antagonized acetylcholine- induced colonic responses. Butoxycarbonyl (BOC)-CCK31-33-amide increased basal colonic motility, but did not alter CCK-OP-induced responses at doses of 0.1 and 0.2 mg/Kg. Dibutyryl-cGMP at a dose of 0.1 mg/Kg did not affect basal motility or CCK-OP-induced contractions. At a dose of 1.0 mg/kg it increased basal colonic motility but did not affect CCK-OP-induced contractions. Pentagastrin increased colonic motor activity only at a dose of 5 micrograms/Kg, i.a., a much higher dose than effective doses of CCK-OP. The mechanism of CCK-OP-induced colonic motor effects also was determined. Atropine sulfate, 100 micrograms/Kg, i.v. significantly reduced both intraarterial acetylcholine-and CCK-OP-induced maximum colonic contractions. Tetrodotoxin, at intravenous doses that completely block neuronal activity, did not affect maximum acetylcholine-induced contractions but practically eliminated maximum CCK-OP-induced maximum colonic responses. In conclusion, intraarterial CCK-OP produces circular muscle contraction of the canine proximal colon that is mediated by stimulation of specific CCK receptors which produce the release of acetylcholine from cholinergic enteric neurons. Proglumide and CBZ-CCK27-32-amide are effective CCK receptor antagonists at these colonic neuronal receptors.     

Neurotensin modulates pacemaker activity in interstitial cells of Cajal from the mouse small intestine

Neurotensin, a tridecapeptide localized in the gut to discrete enteroendocrine cells of the small bowel mucosa, is a hormone that plays an important role in gastrointestinal secretion, growth, and motility. Neurotensin has inhibitory and excitatory effects on peristaltic activity and produces contractile and relaxant responses in intestinal smooth muscle. Our objective in this study is to investigate the effects of neurotensin in small intestinal interstitial cells of Cajal (ICC) and elucidate the mechanism. To determine the electrophysiological effects of neurotensin on ICC, whole-cell patch clamp recordings were performed in cultured ICC from the small intestine. Exposure to neurotensin depolarized the membrane of pacemaker cells and produced tonic inward pacemaker currents. Only neurotensin receptor1 was identified when RT-PCR and immunocytochemistry were performed with mRNA isolated from small intestinal ICC and c-Kit positive cells. Neurotensin-induced tonic inward pacemaker currents were blocked by external Na⁺- free solution and in the presence of flufenamic acid, an inhibitor of non-selective cation channels. Furthermore, neurotensin-induced action is blocked either by treatment with {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122, a phospholipase C inhibitor, or thapsigargin, a Ca²⁺-ATPase inhibitor in ICC. We found that neurotensin increased spontaneous intracellular Ca²⁺ oscillations as seen with fluo4/AM recording. These results suggest that neurotensin modulates pacemaker currents via the activation of non-selective cation channels by intracellular Ca²⁺-release through neurotensin receptor1.     

Spatiotemporal mapping of the motility of the isolated chicken caecum

We studied the caecal contractile activity of the chicken (Gallus gallus) using single caeca that had been cannulated at their proximal and distal ends, and in paired caeca, maintained in situ on excised segments of gut that were cannulated at the colonic and small intestinal ends. Longitudinal and circular contractile patterns were characterised using high-definition spatiotemporal mapping. Low amplitude longitudinal contraction waves of frequency 14.1 cycles/min occurred in the absence of major contractile events. These were termed fast phasic and appeared to be mediated by slow waves. The nature of major spontaneous contractions occurring in the single caecum varied with the level of caecal distension. Type A contractions occurred when the caecum was not distended, originated from variable sites and propagated in both directions. Type B or C contractile events occurred when the caecum was moderately or fully distended, originated from a predominantly distal site and propagated proximally. On diameter maps, each type B event comprised a succession of contractions which had similar propagation speeds, frequency and direction to fast phasic contractions. Type C events were comprised of a succession of higher amplitude contractions with no appreciable propagation. Perfusion of saline via the colon resulted in fluid entering both caeca and the onset of aborad contractions in their proximal canals. Saline was also seen to flow between caeca during contractile events however no saline was seen to enter the small intestine as has been postulated by other workers.     

Intravital microscopy: a new in vivo technique for visualizing and quantifying effects of regulatory peptides on choledochoduodenal junction motility

Using intravital microscopy, we studied the in vivo effects of regulatory peptides on choledochoduodenal junction motility in guinea pigs. During basal and hormone-stimulated periods, intravital microscopy documented rhythmic, asymmetrical, "milking" contractions of the sphincter ductus choledochi (SDC) which occurred independent of sphincter ampullae (SA) contractions or were followed by SA contractions. Cholecystokinin octapeptide (CCK-8) (greater than or equal to 0.01 micrograms/kg) increased the frequency of SDC contractions and at higher doses (greater than or equal to 0.1 microgram/kg) increased the frequency of SA contractions. Pentagastrin (greater than or equal to 1.0 microgram/kg) and secretin (10 micrograms/kg) decreased the contraction frequencies of both sphincters. Biliary manometry demonstrated similar effects of these peptides on the frequency of the SDC and SA contractions, but also showed that CCK-8 (0.1 microgram/kg) increased the amplitude of SDC and SA contractions while pentagastrin (1 microgram/kg) decreased the amplitude of only SDC contractions. Tetrodotoxin and atropine did not affect hormone-induced changes in frequency, but tetrodotoxin reduced the increase in amplitude of contraction caused by CCK-8. We concluded that intravital microscopy provides a sensitive, in vivo technique to visualize and quantify the complex motility of a small structure like the choledochoduodenal junction.     

Curcuma longa Extract Exerts a Myorelaxant Effect on the Ileum and Colon in a Mouse Experimental Colitis Model, Independent of the Anti-Inflammatory Effect

Background

Curcuma has long been used as an anti-inflammatory agent in inflammatory bowel disease. Since gastrointestinal motility is impaired in inflammatory states, the aim of this work was to evaluate if Curcuma Longa had any effect on intestinal motility.

Methods

The biological activity of Curcuma extract was evaluated against Carbachol induced contraction in isolated mice intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Spontaneous contractions and the response to Carbachol and Atropine of ileum and colon were studied after colitis induction and Curcuma administration.

Results

Curcuma extract reduced the spontaneous contractions in the ileum and colon; the maximal response to Carbachol was inhibited in a non-competitive and reversible manner. Similar results were obtained in ileum and colon from Curcuma fed mice. DSS administration decreased the motility, mainly in the colon and Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet, but a prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced contractions.

Conclusions

Curcuma extract has a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The indirect effect is reversible and non-competitive with the cholinergic agent. These results suggest the use of curcuma extract as a spasmolytic agent.     

Brain CCKA receptors mediate the colonic motor response to feeding in dogs

The influence of central vs. peripheral administration of specific type A and type B CCK receptor antagonists (L364,718 and L365,260, respectively) on colonic motor hyperactivity induced by feeding and CCK8 was investigated in dogs with strain-gauge transducers implanted on the proximal and transverse colon. Intravenous injection of L364,718 (5 and 10 micrograms/kg) reduced by 26.2% and 80.1%, respectively, the 0-4-h postprandial increase in colonic motor index; at similar doses L365,260 had no effect. Intracerebroventricular administration of L364,718, at a dose (1 microgram/kg) not active by the IV route, significantly reduced (p less than 0.01) by 67.5% the feeding-induced colonic hyperactivity. In contrast, L365,260 (1-10 micrograms/kg ICV) injected was inactive. Increase in colonic motility produced by intravenous CCK8 infusion (1 microgram/kg/h) was suppressed by previous ICV and IV administration of L364,718 at doses of 1 and 10 micrograms/kg, respectively, while L365,260 was inactive at similar doses. It is concluded that CCK8 released after a meal is responsible for the postprandial increase in colonic motility and that these effects may be mediated through activation of central CCKA receptors.     

Functional and neurochemical evidence that neurotensin-induced release of acetylcholine from Auerbach's plexus of guinea-pig ileum is presynaptically controlled via α2-adrenoceptors

The effect of neurotensin (NT) on [³H]acetylcholine release and contraction from isolated longitudinal muscle strip of guinea-pig ileum was examined. Neurotensin dose-dependently enhanced the release of [³H]-acetylcholine. This effect of neurotensin was inhibited by stimulation of ₂-adrenoceptors: noradrenaline, clonidine, xylazine or dexmedetomidine (₂-adrenoceptor agonists) inhibited neurotensin-induced release of acetycholine (ACh) as well as the contractions, while CH-38083 or yohimbine (₂-adrenoceptor antagonist) prevented this inhibitory effect. Our findings suggest that neurotensin may play a neuromodulatory role in the regulation of cholinergic neuronal activity in the gut and this modulatory effect is continuously controlled by the tonic activity of the sympathetic nervous system: endogenous noradrenaline release is capable of reducing the release of ACh and the consequent contraction of the gut enhanced by neurotensin.     

Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility

Organ–organ crosstalk is involved in homeostasis. Gastrointestinal symptoms are common in patients with renal failure. The aim of this study was to elucidate the relationship between gastrointestinal motility and gastrointestinal symptoms in chronic kidney disease. We performed studies in C57BL/6 mice with chronic kidney disease after 5/6 nephrectomy. Gastrointestinal motility was evaluated by assessing the ex vivo responses of ileum and distal colon strips to electrical field stimulation. Feces were collected from mice, and the composition of the gut microbiota was analyzed using 16S ribosomal RNA sequencing. Mice with chronic kidney disease after 5/6 nephrectomy showed a decreased amount of stool, and this constipation was correlated with a suppressed contraction response in ileum motility and decreased relaxation response in distal colon motility. Spermine, one of the uremic toxins, inhibited the contraction response in ileum motility, but four types of uremic toxins showed no effect on the relaxation response in distal colon motility. The 5/6 nephrectomy procedure disturbed the balance of the gut microbiota in the mice. The motility dysregulation and constipation were resolved by antibiotic treatments. The expression levels of interleukin 6, tumor necrosis factor-α, and iNOS in 5/6 nephrectomy mice were increased in the distal colon but not in the ileum. In addition, macrophage infiltration in 5/6 nephrectomy mice was increased in the distal colon but not in the ileum. We found that 5/6 nephrectomy altered gastrointestinal motility and caused constipation by changing the gut microbiota and causing colonic inflammation. These findings indicate that renal failure was remarkably associated with gastrointestinal dysregulation.     

Action of the newly discovered mammalian tachykinins, substance K and neuromedin K, on gastroduodenal motility of anesthetized dogs

The present experiments examined the local effects of two new mammalian tachykinins isolated from porcine spinal cord, substance K and neuromedin K, on gastroduodenal motility of anesthetized dogs. Tachykinins were injected through the gastroepiploic and cranial pancreaticoduodenal arteries at concentrations ranging from 1 to 100 ng/ml. Substance K, neuromedin K and substance P increased gastroduodenal smooth muscle contractions in a dose-dependent manner. The contractile response of the gastric antrum to newly discovered tachykinins was not as long-lasting as that to substance P. The potencies of various tachykinins on contractile responses showed the following rank order of potencies: physalaemin = eledoisin = substance P greater than substance K = neuromedin K in gastric smooth muscle; physalaemin = substance P = eledoisin greater than substance K = neuromedin K in the duodenal smooth muscle. Administration of atropine (100-200 micrograms/kg) inhibited the effect of tachykinins both in the gastric antrum and in the proximal duodenum. These results indicate that substance K and neuromedin K could act as transmitters or as modulators of neuronal activity influencing gastroduodenal motility.     

Role of extrinsic innervation in modulating nitrergic transmission in the canine ileocolonic region

The human colon can dilate, often to life-threatening proportions. Our aim was to explore nitrergic mechanisms underlying colonic dilation in conscious dogs with enterically isolated ileocolonic loops either extrinsically innervated (n = 4) or extrinsically denervated (n = 4). We recorded phasic pressures in ileum and ileocolonic sphincter (ICS), colonic tone, compliance, and relaxation during ileal distension. By NADPH-diaphorase histochemistry, we assessed effects of extrinsic denervation and enteric isolation on nitrergic fibers. Extrinsic denervation increased phasic pressures in ileum, ICS, and colon and abolished ICS and colonic relaxation in response to ileal distension. The nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine (L-NNA) increased phasic pressures at all sites and ICS tone but did not abolish colonic relaxation during ileal distension in innervated loops. L-NNA reduced compliance and induced colonic high-amplitude propagated contractions in denervated loops. The NOS substrate donor L-arginine reversed effects of L-NNA. The number of NADPH-diaphorase fibers increased in both enterically isolated preparations. Nonnitrergic extrinsic nerve pathways mediate reflex colonic relaxation during ileal distension. Enteric isolation augments the number of NOS fibers, an effect not modified by extrinsic denervation.     

Contractile activity of duodenum, jejunum, and ileum at psychogenic stress in rabbits before and after muscarinic or nicotinic cholinoceptor blockade

In chronic experiments on rabbits, myoelectric activity (contractile activity index) in distal part of the duodenum, proximal and distal parts of the jejunum and proximal part of the ileum was studied under psychogenic stress caused by rigid fastening rabbit to a table in supine position. In duodenum, the stressor impact rendered stimulating, and in an ileum--inhibitory influence on their motility. In a jejunum the inhibition with the subsequent stimulation was observed, the latter being more expressed in a proximal part of the intestine. The proximo-distal gradient of exitatory and inhibitory influences of the psychogenic stress on contractile activity of the small bowel was revealed: in distal direction, inhibitory influences strengthen and stimulatory ones weaken. The muscarinic receptor blockade abolished increase of the duodenal and jejunal contractile activity obsereved in the control. The nicotinic cholinoceptor blockade abolished increase of the duodenal contractile activity in the 1-st phase of the stressor response and did not exclude an increase of the duodenal contractile activity in the 2-nd phase of the response. Muscarinic or nicotinic blockade did not influence the manifestation of the inhibitory reaction of proximal part of the ileum. In the period after release of the animal, the duodenal and jejunal contractile activity exeeded its initial level. This exeeding did not preserve after muscarinic cholinoceptor blockade but did preserve after nicotinic one in duodenum and proximal jejunum. The received data allow to conclude, that produced by the stress increase of the contractile activity of the distal part of duodenum, proximal and distal parts of jejunum produced by the stress, as well as exceeding the initial contractile activity level in the period after release of an animal, are mediated by cholinergic effector neurones of the enteric nervous system.     

Effect of corticosterone, hydrocortisone and prostaglandin fatty acid precursors on the spontaneous motility of the uterus isolated from ovariectomized rats

The effect of corticosterone (CC, 0.4 and 1 microgram/ml) and of hydrocortisone (HC, 20 and 40 micrograms/ml) on the spontaneous motility and on prostaglandin (PG) generation in the uterus from ovariectomized rats, was studied. Both concentrations of CC depressed significantly the frequency of contractions but the isometric developed tension was affected only by the higher dose. HC significantly inhibited the isometric developed tension at both concentrations whereas the contractile frequency was only depressed by the higher one. The CC-inhibited motility was accompanied by a reduction in the amount of PGs released from the uterus into the bath solution. In addition, the influences of arachidonic acid (AA), linoleic acid (LA) and gamma-linolenic acid (alpha-LA) - 1 or 2 micrograms/ml - on the depression evoked by CC, were also explored. The fatty acids had no effect on the spontaneous uterine motility except in the case of alpha-LA at 1 microgram/ml. alpha-LA completely blocked the CC-evoked reduction of both tension and frequency; AA (1 microgram/ml) elicited a reversion only on frequency whereas LA had no effect at all. This reversion by a fatty acid PG-precursor might indicate that CC is able to diminish substrate availability for PG synthesis in the rat uterus.     

Interaction of neurotensin with caerulein or secretin on digestive tract growth in rats

Because neurotensin may potentiate exocrine pancreatic secretory responses to cholecystokinin and secretin, we examined interactions of neurotensin with caerulein or secretin on growth of pancreas, stomach, small intestine, and colon. Rats were injected with saline, neurotensin (100 μg/kg), caerulein (0.67 μg/kg), secretin (100 μg/kg), or neurotensin plus caerulein or secretin every 8 h for 5 days. Pancreas, stomach, small intestine, and colon were weighed and assayed for DNA, protein, and digestive enzymes. Although neurotensin increased pancreatic weight (P < 0.01), DNA (P < 0.01), and protein content (P < 0.05) by 20–30%, it had less than additive effects on responses to caerulein and secretin. Neurotensin had no effects on pancreatic enzymes or on responses to caerulein or secretin. Neurotensin alone had no effects on growth of the oxyntic gland area or antrum but inhibited increases in antral weight, DNA, and protein caused by secretin. Neurotensin increased small intestine weight (9%, P < 0.05) and protein content (23%, P < 0.01). Secretin also increased weight (22%), DNA (29%), and protein content (48%) of the small intestine (all P < 0.01), but neurotensin and secretin together had less than additive effects. Our results suggest that neurotensin inhibits rather than potentiates certain growth effects of caerulein or secretin on the pancreas and other organs.     

Evaluation of the effects of pentagastrin, gastrin and pancreatic glucagon on cell proliferation in the rat gastrointestinal tract

The effects of six injections of a range of doses (100-1000 micrograms/kg bodyweight) of pentagrastrin and single injection of a range of doses of porcine gastrin (10-40 micrograms/kg bodyweight) and pancreatic glucagon (25-100 micrograms/kg bodyweight) on cell proliferation in the intestine of fasted rats has been investigated. The end-point employed included the measurement of 14C leucine incorporation and thymidine-derived tritium content of the body of the stomach, duodenum, jejunum, ileum and colon. The carbon 14 and tritium content per microgram of tissue in triplicate samples of fifty individually dissected crypts of glands were determined. From these data and the wet weight of the washed, blotted, intestinal segments, values for crypts/micrograms tissue and crypts/segment were calculated. The results demonstrated that pentagastrin at physiological doses decreased cell proliferation slightly in stomach, while gastrin and glucagon were without effect. In the small intestine, pentagastrin and gastrin were without significant effect with the exception that they increased the weight of the duodenum. In contrast, a high physiological dose of glucagon increased DNA and protein synthesis throughout the small bowel, but particularly in the ileum. Pharmacological doses of pentagastrin and all doses of gastrin appeared to increase cell proliferation in the colon although the possibility could not be excluded that this was due to stimulation of precursor uptake. Gastrin also increased colonic weight. Glucagon had no effects in the colon. These observations are compatible with the hypothesis that (i) the primary effects of gastrin and pentagastrin on the proximal intestine are as secretogogues and effects on cell proliferation may be secondary, (ii) gastrin and pentagastrin at physiological levels do not stimulate small intestinal cell proliferation, however glucagon does, and (iii) gastrin at physiological levels and pentagastrin at pharmacological levels may stimulate cell proliferation in the colon.     

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.     

Inhibitory and excitatory mechanisms of neurotensin action in canine intestinal circular muscle in vitro.

The effect of neurotensin on canine ileal circular muscle devoid of myenteric plexus was investigated using single and double sucrose gap techniques. Similar results were obtained with microelectrode techniques. Neurotensin caused a temperature-sensitive and dose-dependent biphasic response, an initial hyperpolarization associated with inhibition of contractile activity, followed by an excitatory phase, usually consisting of spike discharge and tonic and phasic contractions, for which depolarization was not required. Neither response was affected by tetrodotoxin, phentolamine, propranolol, or atropine. The hyperpolarization was associated with decreased membrane resistance, blocked by 10(-7) M apamin, and converted to tonic depolarization by apamin (10(-6) M). Tachyphylaxis to neurotensin occurred when the stimulation interval was less than 20 min. After Ca2+ depletion, depolarization was observed instead of the hyperpolarization; this depolarization was not affected by nitrendipine and was gradually abolished with repetitive stimulation at 20-min intervals. When Ca2+ was present, nifedipine did not alter the hyperpolarizing phase of the response but inhibited spiking and blocked all contractions. The excitatory phase of the response was enhanced by Bay K-8644. Neuromedin N elicited a response identical with that of neurotensin. The responses of the two peptides were completely cross tachyphylactic. Inhibitory junction potentials were not affected by neurotensin tachyphylaxis. It is concluded that neurotensin and neuromedin N activate apamin-sensitive, calcium-dependent potassium channels in circular muscle, causing membrane hyperpolarization and inhibition of muscle contraction. Release of intracellular calcium is involved in the activation of these potassium channels.(ABSTRACT TRUNCATED AT 250 WORDS)