Prophylactic and therapeutic benefits of COX-2 inhibitor on motility dysfunction in bowel obstruction: roles of PGE₂ and EP receptors

We reported previously that mechanical stretch in rat colonic obstruction induces cyclooxygenase (COX)-2 expression in smooth muscle cells. The aims of the present study were to investigate whether in vivo treatment with COX-2 inhibitor has prophylactic and therapeutic effects on motility dysfunction in colon obstruction, and if so what are the underlying mechanisms. Partial colon obstruction was induced with a silicon band in the distal colon of 6-8-wk-old Sprague-Dawley rats; obstruction was maintained for 3 days or 7 days. Daily administration of COX-2 inhibitor NS-398 (5 mg/kg) or vehicle was started before or after the induction of obstruction to study its prophylactic and therapeutic effects, respectively. The smooth muscle contractility was significantly suppressed, and colonic transit rate was slower in colonic obstruction. Prophylactic treatment with NS-398 significantly prevented the impairments of colonic transit and smooth muscle contractility and attenuated fecal collection in the occluded colons. When NS-398 was administered therapeutically 3 days after the initiation of obstruction, the muscle contractility and colonic transit still improved on day 7. Obstruction led to marked increase of COX-2 expression and prostaglandin E(2) (PGE(2)) synthesis. Exogenous PGE(2) decreased colonic smooth muscle contractility. All four PGE(2) E-prostanoid receptor types (EP1 to EP4) were detected in rat colonic muscularis externa. Treatments with EP1 and EP3 antagonists suppressed muscle contractility in control tissue but did not improve contractility in obstruction tissue. On the contrary, the EP2 and EP4 antagonists did not affect control tissue but significantly restored muscle contractility in obstruction. We concluded that our study shows that COX-2 inhibitor has prophylactic and therapeutic benefits for motility dysfunction in bowel obstruction. PGE(2) and its receptors EP2 and EP4 are involved in the motility dysfunction in obstruction, whereas EP1 and EP3 mediate PGE(2) regulation of colonic smooth muscle contractile function in normal state.     

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.     

Trypanosoma cruzi: preliminary investigation of NADH-positive and somatostatin-immunoreactive neurons in the myenteric plexus of the mouse colon during the infection

In this paper, the distribution of NADH-positive and somatostatin (SOM) immunoreactive neurons in the myenteric plexus of the colon of mice infected with Trypanosoma cruzi was studied. Ten young, male, BALB/c mice were inoculated with the Y strain of T. cruzi, 60 days previously (chronic phase of the infection). Another 10 mice were uninfected controls. Distal and proximal colonic neurons from five chronically infected mice and their controls were stained using the NADH-diaphorase method. Quantitative results showed a significant decrease of 39% in the number of neurons in the proximal colon of infected mice and 58% in the distal colon (p<0.05). SOM was localized in five animals from each group by light microscopy, using an indirect immunofluorescence technique. It was observed that there were far fewer nerve cells and fibres and less intensely stained neuron bodies and varicose SOM-positive nerve fibres in both, control and chronic infected mice. These findings could be related to the disturbances in intestinal motility observed in patients in the chronic phase of Chagas' disease.     

Restraint stress stimulates colonic motility via central corticotropin-releasing factor and peripheral 5-HT3 receptors in conscious rats

Although restraint stress accelerates colonic transit via a central corticotropin-releasing factor (CRF), the precise mechanism still remains unclear. We tested the hypothesis that restraint stress and central CRF stimulate colonic motility and transit via a vagal pathway and 5-HT(3) receptors of the proximal colon in rats. (51)Cr was injected via the catheter positioned in the proximal colon to measure colonic transit. The rats were subjected to a restraint stress for 90 min or received intracisternal injection of CRF. Ninety minutes after the administration of (51)Cr, the entire colon was removed, and the geometric center (GC) was calculated. Four force transducers were sutured on the proximal, mid, and distal colon to record colonic motility. Restraint stress accelerated colonic transit (GC of 6.7 +/- 0.4, n=6) compared with nonrestraint controls (GC of 5.1 +/- 0.2, n=6). Intracisternal injection of CRF (1.0 microg) also accelerated colonic transit (GC of 7.0 +/- 0.2, n=6) compared with saline-injected group (GC of 4.6 +/- 0.5, n=6). Restraint stress-induced acceleration of colonic transit was reduced by perivagal capsaicin treatment. Intracisternal injection of CRF antagonists (10 microg astressin) abolished restraint stress-induced acceleration of colonic transit. Stimulated colonic transit and motility induced by restraint stress and CRF were significantly reduced by the intraluminal administration of 5-HT(3) antagonist ondansetron (5 x 10(-6) M; 1 ml) into the proximal colon. Restraint stress and intracisternal injection of CRF significantly increased the luminal content of 5-HT of the proximal colon. It is suggested that restraint stress stimulates colonic motility via central CRF and peripheral 5-HT(3) receptors in conscious rats.     

Electroacupuncture at ST-36 accelerates colonic motility and transit in freely moving conscious rats

Acupuncture is useful for functional bowel diseases, such as constipation and diarrhea. However, the mechanisms of beneficial effects of acupuncture on colonic function have scarcely ever been investigated. We tested the hypothesis that electroacupuncture (EA) at ST-36 stimulates colonic motility and transit via a parasympathetic pathway in conscious rats. Hook-shaped needles were inserted at bilateral ST-36 (lower limb) or BL-21 (back) and electrically stimulated at 10 Hz for 20 min. We also studied c-Fos expression in response to EA at ST-36 in Barrington's nucleus of the pons. EA at ST-36, but not BL-21, significantly increased the amplitude of motility at the distal colon. The calculated motility index of the distal colon increased to 132 +/- 9.9% of basal levels (n = 14, P < 0.05). In contrast, EA at ST-36 had no stimulatory effects in the proximal colon. EA at ST-36 significantly accelerated colonic transit [geometric center (GC) = 6.76 +/- 0.42, n = 9, P < 0.001] compared with EA at BL-21 (GC = 5.23 +/- 0.39, n = 7). The stimulatory effect of EA at ST-36 on colonic motility and transit was abolished by pretreatment with atropine. EA-induced acceleration of colonic transit was also abolished by extrinsic nerve denervation of the distal colon (GC = 4.69 +/- 0.33, n = 6). The number of c-Fos-immunopositive cells at Barrington's nucleus significantly increased in response to EA at ST-36 to 8.1 +/- 1.1 cells/section compared with that of controls (2.4 +/- 0.5 cells/section, n = 3, P < 0.01). It is concluded that EA at ST-36 stimulates distal colonic motility and accelerates colonic transit via a sacral parasympathetic efferent pathway (pelvic nerve). Barrington's nucleus plays an important role in mediating EA-induced distal colonic motility in conscious rats.     

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.     

Mice lacking the dopamine transporter display altered regulation of distal colonic motility

The mechanisms by which dopamine (DA) influences gastrointestinal (GI) tract motility are incompletely understood and complicated by tissue- and species-specific differences in dopaminergic function. To improve the understanding of DA action on GI motility, we used an organ tissue bath system to characterize motor function of distal colonic smooth muscle segments from wild-type and DA transporter knockout (DAT -/-) mice. In wild-type mice, combined blockade of D(1) and D(2) receptors resulted in significant increases in tone (62 +/- 9%), amplitude of spontaneous phasic contractions (167 +/- 24%), and electric field stimulation (EFS)-induced (40 +/- 8%) contractions, suggesting that endogenous DA is inhibitory to mouse distal colonic motility. The amplitudes of spontaneous phasic and EFS-induced contractions were lower in DAT -/- mice relative to wild-type mice. These differences were eliminated by combined D(1) and D(2) receptor blockade, indicating that the inhibitory effects of DA on distal colonic motility are potentiated in DAT -/- mice. Motility index was decreased but spontaneous phasic contraction frequency was enhanced in DAT -/- mice relative to wild-type mice. The fact that spontaneous phasic and EFS-induced contractile activity were altered by the lack of the DA transporter suggests an important role for endogenous DA in modulating motility of mouse distal colon.     

Effects of a cannabinoid receptor agonist on colonic motor and sensory functions in humans: a randomized, placebo-controlled study

Cannabinoid receptors (CBR) are located on cholinergic neurons in the brain stem, stomach, and colon. CBR stimulation inhibits motility in rodents. Effects in humans are unclear. Dronabinol (DRO), a nonselective CBR agonist, inhibits colonic motility and sensation. The aim of this study was to compare effects of DRO and placebo (PLA) on colonic motility and sensation in healthy volunteers. Fifty-two volunteers were randomly assigned (double-blind) to a single dose of 7.5 mg DRO or PLA postoperative with concealed allocation. A balloon-manometric assembly placed into the descending colon allowed assessment of colonic compliance, motility, tone, and sensation before and 1 h after oral ingestion of medication, and during fasting, and for 1 h after 1,000-kcal meal. There was an overall significant increase in colonic compliance (P = 0.045), a borderline effect of relaxation in fasting colonic tone (P = 0.096), inhibition of postprandial colonic tone (P = 0.048), and inhibition of fasting and postprandial phasic pressure (P = 0.008 and 0.030, respectively). While DRO did not significantly alter thresholds for first gas or pain sensation, there was an increase in sensory rating for pain during random phasic distensions at all pressures tested and in both genders (P = 0.024). In conclusion, in humans the nonselective CBR agonist, DRO, relaxes the colon and reduces postprandial colonic motility and tone. Increase in sensation ratings to distension in the presence of relaxation of the colon suggests central modulation of perception. The potential for CBR to modulate colonic motor function in diarrheal disease such as irritable bowel syndrome deserves further study.     

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats

Enterochromaffin (EC) cells of the epithelial cells release 5-HT into the lumen, as well as basolateral border. However, the physiological role of released 5-HT into the lumen is poorly understood. Concentrations of 5-HT in the colonic mucosa, colonic lumen, and feces were measured by HPLC in rats. To investigate whether intraluminal 5-HT accelerates colonic transit, 5-HT and (51)Cr were administered into the lumen of the proximal colon, and colonic transit was measured. To investigate whether 5-HT is released into the lumen, we used an ex vivo model of isolated vascularly and luminally perfused rat proximal colon. To investigate whether luminal 5-HT is involved in regulating stress-induced colonic motility, the distal colonic motility was recorded under the stress loading, and a 5-HT(3) receptor antagonist (ondansetron, 10(-6) M, 0.5 ml) was administered intraluminally of the distal colon. Tissue content of 5-HT in the proximal colon (15.2 +/- 4.3 ng/mg wet tissue) was significantly higher than that in the distal colon (3.3 +/- 0.7 ng/mg wet tissue), while fecal content and luminal concentration of 5-HT was almost the same between the proximal and distal colon. Luminal administration of 5-HT (10(-6)-10(-5) M) significantly accelerated colonic transit. Elevation of intraluminal pressure by 10 cmH(2)O significantly increased the luminal concentration of 5-HT but not the vascular concentration of 5-HT. Stress-induced stimulation of the distal colonic motility was significantly attenuated by the luminal administration of ondansetron. These results suggest that luminally released 5-HT from EC cells plays an important role in regulating colonic motility in rats.     

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.     

slc26a3 (dra)-deficient mice display chloride-losing diarrhea, enhanced colonic proliferation, and distinct up-regulation of ion transporters in the colon

Mutations in the SLC26A3 (DRA (down-regulated in adenoma)) gene constitute the molecular etiology of congenital chloride-losing diarrhea in humans. To ascertain its role in intestinal physiology, gene targeting was used to prepare mice lacking slc26a3. slc26a3-deficient animals displayed postpartum lethality at low penetrance. Surviving dra-deficient mice exhibited high chloride content diarrhea, volume depletion, and growth retardation. In addition, the large intestinal loops were distended, with colonic mucosa exhibiting an aberrant growth pattern and the colonic crypt proliferative zone being greatly expanded in slc26a3-null mice. Apical membrane chloride/base exchange activity was sharply reduced, and luminal content was more acidic in slc26a3-null mouse colon. The epithelial cells in the colon displayed unique adaptive regulation of ion transporters; NHE3 expression was enhanced in the proximal and distal colon, whereas colonic H,K-ATPase and the epithelial sodium channel showed massive up-regulation in the distal colon. Plasma aldosterone was increased in slc26a3-null mice. We conclude that slc26a3 is the major apical chloride/base exchanger and is essential for the absorption of chloride in the colon. In addition, slc26a3 regulates colonic crypt proliferation. Deletion of slc26a3 results in chloride-rich diarrhea and is associated with compensatory adaptive up-regulation of ion-absorbing transporters.     

Mechanisms of polymicrobial sepsis-induced ileus

Sepsis frequently occurs after hemorrhage, trauma, burn, or abdominal surgery and is a leading cause of morbidity and mortality in severely ill patients. We performed experiments to delineate intestinal molecular and functional motility consequences of polymicrobial sepsis in the clinically relevant cecal ligation and puncture (CLP) sepsis model. CLP was performed on male Sprague-Dawley rats. Gastrointestinal transit, colonic in vivo pressure recordings, and in vitro muscle contractions were recorded. Histochemistry was performed for macrophages, monocytes, and neutrophils. Inflammatory gene expressions were quantified by real-time RT-PCR. CLP delayed gastrointestinal transit, decreased colonic pressures, and suppressed in vivo circular muscle contractility of the jejunum and colon over a 4-day period. A leukocytic infiltrate of monocytes and neutrophils developed over 24 h. Real-time RT-PCR demonstrated a significant temporal elevation in IL-6, IL-1beta, monocyte chemoattractant protein-1, and inducible nitric oxide synthase, with higher expression levels of IL-6 and inducible nitric oxide synthase in colonic extracts compared with small intestine. Polymicrobial CLP sepsis induces a complex inflammatory response within the intestinal muscularis with the recruitment of leukocytes and elaboration of mediators that inhibit intestinal muscle function. Differences were elucidated between endotoxin and CLP models of sepsis, as well as a heterogeneous regional response of the gastrointestinal tract to CLP. Thus the intestine is not only a source of bacteremia but also an important target of bacterial products with major functional consequences to intestinal motility and the generation of cytokines, which participate in the development of multiple organ failure.     

Neuropeptide FF receptors exert contractile activity via inhibition of nitric oxide release in the mouse distal colon

Neuropeptide FF (NPFF) and NPVF, two closely NPFF related peptides, have different affinities for the two NPFF receptors (NPFF1 and NPFF2). To assess the peripheral effects of NPFF receptors in the gastrointestinal tract motility, NPFF and NPVF were tested in the mouse isolated distal colon. Both NPFF (1-15 microM) and NPVF (1-15 microM) dose-dependently caused significant colonic contractions. Pre-treatment with the putative NPFF antagonist, BIBP3226 (30 microM) abolished the contractile responses to the two neuropeptides (3 microM). They had no additional contractile activities in colonic preparations contracted by Nomega-nitro-L-arginine (30 microM). Moreover, the contractions of these two neuropeptides were weakened by L-arginine (2 mM). The responses to NPFF (5 microM) and NPVF (5 microM) were not modified by atropine or naloxone (1 microM). Furthermore, NPFF (1 microM) and NPVF (1 microM) did not influence the contractive responses to acetylcholine (0.1-10 microM), morphine (1 microM) or nociceptin (0.1 microM). These data suggest that NPFF and NPVF cause contractions of the mouse distal colon via their NPFF receptors and this effect is mediated by NO but not by cholinergic pathways, independently from opioid system. In addition, the isolated bioassay may be applied as a simple parameter to characterize the potential NPFF agonists and antagonists.     

Gastrointestinal Motility Monitor (GIMM)

The Gastrointestinal Motility Monitor (GIMM; Catamount Research and Development; St. Albans, VT) is an in vitro system that monitors propulsive motility in isolated segments of guinea pig distal colon. The complete system consists of a computer, video camera, illuminated organ bath, peristaltic and heated water bath circulating pumps, and custom GIMM software to record and analyze data. Compared with traditional methods of monitoring colonic peristalsis, the GIMM system allows for continuous, quantitative evaluation of motility. The guinea pig distal colon is bathed in warmed, oxygenated Krebs solution, and fecal pellets inserted in the oral end are propelled along the segment of colon at a rate of about 2 mm/sec. Movies of the fecal pellet proceeding along the segment are captured, and the GIMM software can be used track the progress of the fecal pellet. Rates of propulsive motility can be obtained for the entire segment or for any particular region of interest. In addition to analysis of bolus-induced motility patterns, spatiotemporal maps can be constructed from captured video segments to assess spontaneous motor activity patterns. Applications of this system include pharmacological evaluation of the effects of receptor agonists and antagonists on propulsive motility, as well as assessment of changes that result from pathophysiological conditions, such as inflammation or stress. The guinea pig distal colon propulsive motility assay, using the GIMM system, is straightforward and simple to learn, and it provides a reliable and reproducible method of assessing propulsive motility.Download video file.^{(51M, mov)}     

β3肾上腺素受体介导多巴胺对大鼠远端结肠运动的抑制作用

目的研究多巴胺（DA）对大鼠结肠运动影响的机制。方法采用离体组织灌流方法记录大鼠远端结肠自发性节律运动,观察DA的作用以及阻断剂的影响,再用反转录实时多聚酶链反应（real time RT-PCR）检测受体基因的表达。结果DA（≥1.0×10-5mol/L）对结肠远端（紧接肛门淋巴结近端）离体纵行肌条（2.0 mm×10 mm）的运动具有抑制作用,多巴胺受体阻断剂（D1受体阻断剂SCH23390,1.0×10-7mol/L,D2受体阻断剂Sulpide,1.0×10-7mol/L）不能阻断多巴胺的抑制效应,但加入β3受体抑制剂cyanopindolol（7.5×10-7mol/L）,DA的抑制作用显著减弱。real time RT-PCR检测发现β1、β2、β3受体mRNA在远端结肠均有表达。结论DA可通过β3受体发挥对远端结肠运动的抑制作用。     

Small intestinal manometry

Gastrointestinal motility is an integrated process including myoelectrical and contractile activity, tone, compliance and transit. The techniques for the assessment of gastrointestinal motility are multiple and all have their advantages and disadvantages. In the case of suspected abnormal upper gut transit, gastric and small bowel transit scintigraphy followed by small intestinal (antroduodenojejunalileal) manometry is recommended. Small bowel manometry can identify patterns suggestive of myopathy, neuropathy or obstruction. Information on procedures, indications, significance, pitfalls and guidelines for small bowel manometry is provided in this paper. In this context the potentials of small intestinal manometry for scientific experimental study of neurohumoral agents, such as serotonin receptor agonists and antagonists, on small intestinal motility is presented.     

Localization of CB1-cannabinoid receptor immunoreactivity in the porcine enteric nervous system

Cannabis has been used for centuries in the medicinal treatment of gastrointestinal disorders. Endogenous cannabinimimetic substances such as 2-arachidonylglycerol have been isolated from gut homogenates and CB1-cannabinoid binding sites have been identified in small intestine. In this study, CB1-cannabinoid receptors (CB1-R) were immunohistochemically localized within the enteric nervous system of the pig, an omnivorous species whose digestive tract is functionally similar to humans. Two anti-CB1-R antisera, raised against N-terminal epitopes in the human CB1-R, were employed to localize receptor immunoreactivity by secondary immunofluorescence. CB1-R immunoreactivity was observed in the myenteric and submucosal ganglionated plexuses of porcine ileum and colon. In the ileum, all CB1-R-immunoreactive neurons coexpressed immunoreactivity to the cholinergic marker, choline acetyltransferase (ChAT). CB1-R/ChAT-immunoreactive neurons appeared to be in close apposition to ileal Peyer's patches, submucosal blood vessels, and intestinal crypts. In the distal colon, CB1-R-immunoreactive neurons also expressed immunoreactivity to ChAT, albeit less frequently than in ileum. Immunoreactivity to vasoactive intestinal peptide or nitric oxide synthase was not colocalized in ileal or colonic CB1-R-immunoreactive neurons. These studies indicate that CB1-R are present in cholinergic neurons in the porcine enteric nervous system. The potential roles of these receptors in intestinal motility and epithelial transport, host defense and visceral pain transmission are discussed.     

Mechanism of action of neurotensin at the ileocecal sphincter region

Neurotensin, a neuropeptide identified in the distal small intestine, plays an unclear role in ileocecal sphincter regional function. The purpose of this study was to determine the effect and mechanism of action of neurotensin on the feline ileocecal sphincter (ICS), proximal colon, and distal ileum. Intraluminal pressures were recorded at these sites in anesthetized cats after superior mesenteric artery injection of neurotensin. Dose dependent tonic and phasic contractions were seen at all sites. Peak pressure responses were seen at the maximal dose used and were greater for the ICS than the distal ileum and the proximal colon. The threshold dose for peak pressures for neurotensin was 0.05 microgram/kg for all sites with the maximal peak pressures occurring at the maximal dose used (100 micrograms/kg). The motility index (MI [number of contractions x mean amplitude of contractions]) was determined for three minutes before and after neurotensin injection. The change in the motility index after neurotensin increased at doses above 0.05 micrograms/kg for the ileum and the ICS and 0.25 microgram/kg for the colon. Maximal responses for the motility index were seen at 1 microgram/kg for the distal ileum, and 10 micrograms/kg for the ICS and the proximal colon, with the greatest response seen at the ICS. Neurotensin-induced ICS relaxation was seen at 1 microgram/kg (50 +/- 10%, p less than 0.01) in 33% of cats. The contractile responses of the distal ileum and the proximal colon were not inhibited by naloxone, trimethaphan, tetrodotoxin, or atropine. The ICS contractile response was decreased by tetrodotoxin by 53%, p less than 0.05. The alpha 2 antagonist, yohimbine reduced the neurotensin induced ICS contraction from 31.6 +/- 3.4 to 21.9 +/- 3.3 mm Hg, p less than 0.05. Prazosin had no effect on neurotensin-induced contractions. In the presence of cimetidine and diphenhydramine, trimethaphan did not affect the neurotensin-induced contractile response at all three sites. However, neurotensin inhibited contractions induced by trimethaphan alone at all three sites. Conclusions: 1. Neurotensin causes a dose-dependent contractile response at the distal ileum, ICS, and proximal colon. 2. Neurotensin has an inhibitory effect at all three sites. 3. The contractile response at the distal ileum and the proximal colon is mediated via smooth muscle receptors. 4. The contractile response of neurotensin at the ICS is mediated partly via alpha 2 receptors and partly via smooth muscle receptors.     

Spawning period and migration of three species of cyprinids in a stream with Mediterranean regimen (SW Spain)

These studies investigated the effects of somatostatin on gastric motility in the rainbow trout. Two experimental models were used, the isolated vascularly-perfused stomach and isolated strips of gastrointestinal smooth muscle. Both models demonstrated that somatostatin can inhibit gastrointestinal motility and may therefore modulate gastric emptying in fish.
In the vascularly-perfused stomach, somatostatin (10–1000 n m ) decreased maximum and baseline intragastric pressure by 10–20% in the presence of stimulatory doses of carbachol or 5-hydroxytryptamine. In addition, somatostatin (1 μ m ) inhibited by 50% the magnitude of spontaneous contractions generated by distension. Somatostatin had little effect on the pressure gradient or contractile frequency. These results suggest that somatostatin may negatively modulate gastric emptying in the rainbow trout.
In isolated gastric smooth muscle strips, somatostatin (100 pmol) inhibited tension stimulated by carbachol (circular orientation of muscle) or 5-hydroxytryptamine (longitudinal orientation). These results correlated with those observed in the vascularly perfused stomach preparation. Somatostatin also decreased tension stimulated by carbachol and 5-hydroxytryptamine in intestinal smooth muscle strips, suggesting that under some conditions somatostatin could increase gastric emptying rate by relaxing intestinal musculature.     

Central 5-hydroxytryptamine (5-HT) mediates colonic motility by hypothalamus oxytocin-colonic oxytocin receptor pathway

Gut-derived 5-hydroxytryptamine (5-HT) is well known for its role in mediating colonic motility function. However, it is not very clear whether brain-derived 5-HT is involved in the regulation of colonic motility. In this study, we used central 5-HT knockout (KO) mice to investigate whether brain-derived 5-HT mediates colonic motility, and if so, whether it involves oxytocin (OT) production in the hypothalamus and OT receptor in the colon. Colon transit time was prolonged in KO mice. The OT levels in the hypothalamus and serum were decreased significantly in the KO mice compared to wild-type (WT) controls. OT increased colonic smooth muscle contraction in both KO and WT mice, and the effects were blocked by OT receptor antagonist and tetrodotoxin but not by hexamethonium or atropine. Importantly, the OT-induced colonic smooth muscle contraction was decreased significantly in the KO mice relative to WT. The OT receptor expression of colon was detected in colonic myenteric plexus of mice. Central 5-HT is involved in the modulation of colonic motility which may modulate through its regulation of OT synthesis in the hypothalamus. Our results reveal a central 5-HT - hypothalamus OT - colonic OT receptor axis, providing a new target for the treatment of brain-gut dysfunction.