Colonic Motility Is Improved by the Activation of 5-HT2B Receptors on Interstitial Cells of Cajal in Diabetic Mice.

BACKGROUND & AIMS: Constipation is commonly associated with diabetes. Serotonin (5-HT), produced predominantly by enterochromaffin (EC) cells via tryptophan hydroxylase 1 (TPH1), is a key modulator of gastrointestinal (GI) motility. However, the role of serotonergic signaling in constipation associated with diabetes is unknown. METHODS: We generated EC cell reporter Tph1-tdTom, EC cell-depleted Tph1-DTA, combined Tph1-tdTom-DTA, and interstitial cell of Cajal (ICC)-specific Kit-GCaMP6 mice. Male mice and surgically ovariectomized female mice were fed a high-fat high-sucrose diet to induce diabetes. The effect of serotonergic signaling on GI motility was studied by examining 5-HT receptor expression in the colon and in vivo GI transit, colonic migrating motor complexes (CMMCs), and calcium imaging in mice treated with either a 5-HT2B receptor (HTR2B) antagonist or agonist. RESULTS: Colonic transit was delayed in males with diabetes, although colonic Tph1+ cell density and 5-HT levels were increased. Colonic transit was not further reduced in diabetic mice by EC cell depletion. The HTR2B protein, predominantly expressed by colonic ICCs, was markedly decreased in the colonic muscles of males and ovariectomized females with diabetes. Ca2+ activity in colonic ICCs was decreased in diabetic males. Treatment with an HTR2B antagonist impaired CMMCs and colonic motility in healthy males, whereas treatment with an HTR2B agonist improved CMMCs and colonic motility in males with diabetes. Colonic transit in ovariectomized females with diabetes was also improved significantly by the HTR2B agonist treatment. CONCLUSIONS: Impaired colonic motility in mice with diabetes was improved by enhancing HTR2B signaling. The HTR2B agonist may provide therapeutic benefits for constipation associated with diabetes.

Satiety testing in diabetic gastroparesis: Effects of insulin pump therapy with continuous glucose monitoring on upper gastrointestinal symptoms and gastric myoelectrical activity.

BACKGROUND: Symptoms induced by caloric or non-caloric satiety test meals and gastric myoelectrical activity (GMA) have not been studied in patients with diabetic gastroparesis (DGP) before and after intense glucose management. AIMS: We determined the effects of continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM) on GI symptoms, volume consumed, and GMA induced by the caloric meal satiety test (CMST) and water load satiety test (WLST) in DGP. METHODS: Forty-five patients with DGP underwent CMST and WLST at baseline and 24 weeks after CSII with CGM. Subjects ingested the test meals until they were completely full. Visual analog scales were used to quantify pre- and postmeal symptoms, and GMA was recorded with cutaneous electrodes and analyzed visually and by computer. KEY RESULTS: At baseline and 24-week visits, nausea, bloating, abdominal discomfort, and fullness were immediately increased after CMST and WLST (Ps < 0.01). The meal volumes ingested were significantly less than normal controls at both visits in almost one-third of the subjects. After the CMST, the percentage 3 cycle per minute GMA increased and bradygastria decreased compared with WLST (Ps < 0.05). After treatment for 24 weeks meal volumes ingested, postmeal symptoms and GMA were no different than baseline. CONCLUSIONS AND INFERENCES: (a) Satiety test meals elicited symptoms of nausea, bloating, and abdominal discomfort; (b) CMST stimulated more symptoms and changes in GMA than WLST; and (c) CSII with CGM for 24 weeks did not improve symptoms, volumes ingested, or GMA elicited by the two satiety test meals in these patients with diabetic GP. Satiety tests in diabetic gastropresis are useful to study acute postprandial symptoms and GMA, but these measures were not improved by intensive insulin therapy.

Abdominal surgery induced gastric ileus and activation of M1-like macrophages in the gastric myenteric plexus: prevention by central vagal activation in rats.

Inflammation plays a role in abdominal surgery (AS)-induced intestinal ileus that is alleviated by electrical vagal stimulation. Intracisternal injection of RX-77368, the stable thyrotropin-releasing hormone agonist, activates dorsal motor nucleus neurons and gastric vagal efferent discharges. We investigated the gastric inflammation induced by AS and the modulation by intracisternal RX-77368 in rats. RX-77368 (50 ng/rat) or saline was injected followed, 1 h later, by laparotomy and small intestinal/cecal manipulation. The sham group had anesthesia alone. After 6 h, gastric emptying (GE) and the inflammation in gastric corpus were determined. AS inhibited GE by 72% vs. control and doubled the number of M1-like macrophage immunoreactive for major histocompatibility complex class II (MHCII; M1 marker) but not for cluster of differentiation 206 (CD206; M2 marker) (MHCII+/CD206-) while there was no change in M2-like macrophages (MHCII-/CD206+). AS increased mRNA levels of interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α) by 1.7- and 1.5-fold, respectively, in the gastric submucosa plus muscle layers and the infiltration of neutrophils labeled by myeloperoxidase by 9.5-fold in the muscularis externa. RX-77368 inhibited AS-related gastric changes while not altering these parameters in the sham group. There was a significant negative correlation between GE and IL-1ß (r = -0.46), TNF-α (r = -0.44), M1 macrophage (r = -0.82), and neutrophils (r = -0.91). The M2-like macrophages and IL-10 expression were unchanged by AS with intracisternal saline or RX-77368. These data indicate that AS activates gastric M1 macrophages and increases proinflammatory cytokines expression, which are prevented by central vagal activation and may contribute to the correlated dampening of postoperative gastric ileus.NEW & NOTEWORTHY MHCII+/CD206- (M1) and MHCII-/CD206+ (M2) constitute two distinct populations of macrophages that are in close apposition to the cholinergic neurons in the rat gastric myenteric plexus (MP). Abdominal surgery (6 h) activates M1 macrophage leading to inflammation in the gastric MP correlated with the delayed gastric emptying, which was abolished by central vagal stimulation via intracisternal injection of RX-77368. Vagal stimulation linked with the cephalic phase may have potential beneficial effects to curtail postoperative gastric ileus.

Motility patterns in mouse colon: gastrointestinal dysfunction induced by anticancer chemotherapy.

Colon cancer is a leading cause of cancer-related death in humans. 5-Fluorouracil (5-FU), a major chemotherapy treatment, has been used for decades to fight numerous types of cancers, including breast, colon, and head and neck carcinomas. Unfortunately, a large proportion of patients treated with 5-FU develop toxicities that include diarrhea, mucositis, neutropenia, and vomiting. While the side effects of 5-FU are well known, the mechanisms underlying the induction of these unpleasant symptoms are poorly understood. The study by McQuade et al. in this issue of Neurogastroenterology & Motility provides important new potential explanations for the gastrointestinal (GI) dysfunction induced by 5-FU. These researchers carefully investigated an overlooked research area in which the symptoms of GI-motility dysfunction maybe due to an effect on the enteric nervous system. McQuade et al. delivered 5-FU treatment to mice and discovered an initial increase in GI transit (associated with acute intestinal inflammation), followed by a slowing in transit. Major differences were noted in characteristics of colonic migrating motor complexes. These effects maybe causally related to deficits in enteric ganglia or neurotransmission. Their study identified specific neurochemical classes of neurons in the myenteric plexus most affected by 5-FU. This is the first study to provide evidence that the functional intrinsic neural pathways within the enteric nervous system are likely impaired by 5-FU, leading to colonic dysmotility. This review will describe major patterns of motor activity in isolated whole mouse colon and how these patterns are modified by anticancer chemotherapy.

[ROLE OF SUBSTRATE ANTIHYPOXANTS IN CORRECTION OF ABNORMALITIES OF MYOELECTRICAL ACTIVITY OF GASTROINTESTINAL TRACT IN VICTIMS WITH SEVERE COMBINED TRAUMA].

The abnormalities of myoelectrical activity of gastrointestinal tract were detected in 80 victims with severe combined trauma. There were observed a decrease of total electrical activity and dyscoordination of electrical activity of sections of gastrointestinal tract. An application of substrate antihypoxants should normalize the indices of myoelectrical activity of gastrointestinal tract. This approach allowed elimination of imbalance of total power between superposed (the stomach, the duodenum) and other sections of gastrointestinal tract. This would remove dyscoordination contraction of the jejunum and the ileum.

[Lymphocyte apoptosis enhancement by the synthetic peptide E in experimental ulcer].

The influence of regulatory peptide type of AFP on the course of experimental ulcer was investigated. It has been shown that activation of apoptosis enhances local necrotic inflammatory reaction, on the one hand, and enables the development of adhesions with on the other.

Epidural plus general anesthesia vs general anesthesia alone for elective aortic surgery: effects on gastric electrical activity and serum gastrin secretion.

BACKGROUND: The aim of this study was to evaluate differences in electrogastrographic activity and serum gastrin secretion in patients subjected to general anesthesia (GA) vs blended anesthesia (BA = GA plus epidural analgesia) for abdominal aortic surgery. METHODS: Thirty-four patients (all males: 28 with abdominal aorta aneurysm, 6 with obstructive aorto-iliac disease; mean age: 68+/-7 years) were randomly assigned either to GA (N.=17) or to BA (N.=17) for abdominal aortic surgery. Each patient was evaluated for serum gastrin secretion at the time of electrogastrography (EGG) 24 h before and after surgery, using ambulatory equipment. Gastrin levels were tested under fasting conditions and after a standard meal. EGG shows gastric electrical activity that parallels gastric motor activity. RESULTS: Before surgery, no significant difference was found for any of the EGG parameters or the serum gastrin integrated value (area under the curve [AUC]) between the two groups of patients. After surgery, an increased frequency of electrical waves (tachygastria) was observed in 22% of those undergoing GA and in 5% of patients undergoing BA. The power ratio (postprandial/fasting total power) was exceedingly high (>4) in 53% of the GA patients and in 11% of the BA patients (P<0.05). The gastrin AUC was 263+/-58 pg/mL in the GA group and 179+/-92 pg/mL in the BA group (P<0.01). CONCLUSIONS: An excess of EGG activity and serum gastrin secretion was observed in patients undergoing GA vs those submitted to BA. Thus, the latter procedure seems to affect gastric function less than GA alone.

The incretin hormones GIP and GLP-1 in diabetic rats: effects on insulin secretion and small bowel motility.

Incretin hormones often display inhibitory actions on gut motility. The aim of this study was to investigate if altered responsiveness to glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) as regards insulin release and small bowel motility could bring further clarity to the pathophysiology of diabetes in the Goto-Kakizaki (GK) rat. The isolated perfused pancreas was studied in male GK and Wistar rats (controls) under euglycemic and hyperglycemic conditions. Glucose-dependent insulinotropic peptide (10 nmol L(-1)) or GLP-1 (10 nmol L(-1)) were added to the medium and perfusate was collected and analysed for insulin. Moreover, GK and Wistar rats were supplied with bipolar electrodes in the small bowel and myoelectric activity was recorded during intravenous administration of GIP (1-400 pmol kg(-1) min(-1)) or GLP-1 (0.1-20 pmol kg(-1) min(-1)). Finally, tissue was collected from GK and Wistar rats for RNA extraction. Under euglycemia, GIP and GLP-1 stimulated the initial insulin response by 10-fold in GK rats (P < 0.05). At later hyperglycemia, the insulin response to GIP and GLP-1 was blunted to about one-third compared with controls (P < 0.05). In the bowel GLP-1 was about 2.6-16.7 times more potent than GIP in abolishing the migrating myoelectric complex in the GK and control rats. Polymerase chain reaction (PCR) showed GIP and GLP-1 receptor gene expression in pancreatic islets and in small bowel. The initially high, but later low insulin responsiveness to stimulation with GIP and GLP-1 along with inhibition of small bowel motility in the GK rat indicates a preserved incretin response on motility in diabetes type 2.

Autoantibodies to calcium channels in type 1 diabetes mediate autonomic dysfunction by different mechanisms in colon and bladder and are neutralized by antiidiotypic antibodies.

Autoantibodies (Abs) directed against L-type voltage-gated calcium channels (VGCCs) have been shown to contribute to autonomic dysfunction of the gastrointestinal tract and bladder in patients with Type 1 diabetes mellitus (T1D). We used a passive transfer model to determine whether the functional activity of the Ab requires crosslinking of channels in colon and bladder and can be neutralized by intravenous immunoglobulin (IVIg). Mice were injected with mono- and divalent F(ab) fragments of patient IgG with anti-VGCC activity and tested for gut and bladder function using a colonic migrating motor complex (MMC) assay and bladder-filling cystometry. The ability of IVIg to neutralize anti-VGCC IgG-mediated autonomic dysfunction was investigated by injection of mice with an equimolar concentration of IVIg prior to T1D IgG injection, or by injection with T1D IgG passed over a sepharose 4B column coupled with F(ab')(2) from IVIg. Passive transfer of T1D IgG and its F(ab')(2) or F(ab) fragments reduced the amplitude of spontaneous colonic motility. In contrast, intact IgG and F(ab')(2,) but not F(ab), produced the urodynamics features of an overactive bladder. T1D IgG-mediated colonic and bladder dysfunction was neutralized in vivo by prior injection of animals with equimolar IVIg. Moreover, anti-VGCC activity was depleted by preabsorption of patient IgG on a IVIg F(ab')(2) column. The activity of anti-VGCC IgG is mediated by the antigen-binding site consistent with a true functional Ab. The pathogenic effect on the bladder requires crosslinking of the channel, whereas monovalent binding of Ab is sufficient for disruption of colon motility. The anti-VGCC Abs are neutralized by antiidiotypic antibodies present in IVIg that may prevent the emergence of these Abs in healthy individuals.

Obestatin inhibits motor activity in the antrum and duodenum in the fed state of conscious rats.

Obestatin is a novel peptide encoded by the ghrelin precursor gene; however, its effects on gastrointestinal motility remain controversial. Here we have examined the effects of obestatin on fed and fasted motor activities in the stomach and duodenum of freely moving conscious rats. We examined the effects of intravenous (IV) injection of obestatin on the percentage motor index (%MI) and phase III-like contractions in the antrum and duodenum. The brain mechanism mediating the action of obestatin on gastroduodenal motility and the involvement of vagal afferent pathway were also examined. Between 30 and 90 min after IV injection, obestatin decreased the %MI in the antrum and prolonged the time taken to return to fasted motility in the duodenum in fed rats given 3 g of chow after 18 h of fasting. Immunohistochemical analysis demonstrated that corticotropin-releasing factor- and urocortin-2-containing neurons in the paraventricular nucleus in the hypothalamus were activated by IV injection of obestatin. Intracerebroventricular injection of CRF type 1 and type 2 receptor antagonists prevented the effects of obestatin on gastroduodenal motility. Capsaicin treatment blocked the effects of obestatin on duodenal motility but not on antral motility. Obestatin failed to antagonize ghrelin-induced stimulation of gastroduodenal motility. These results suggest that, in the fed state, obestatin inhibits motor activity in the antrum and duodenum and that CRF type 1 and type 2 receptors in the brain might be involved in these effects of obestatin on gastroduodenal motility.

Role of activation of cholinergic influences in recovery of electrical activity of the stomach and small intestine during the early postoperative period in rats.

The effects of neostigmine and calcium pantothenate on electrical activity of the stomach and small intestine were studied in chronic experiments on rats after laparotomy with implantation of a probe into the jejunum and electrodes into different portions of the gastrointestinal tract. At the early terms after surgery, stimulation of endogenous acetylcholine release intensified electrical activity of the stomach, duodenum, and jejunum. Treatment with neostigmine and calcium pantothenate did not accelerate the recovery of the migrating myoelectrical complex, but promoted the recovery of the general intensity of action potential generation in the stomach and small intestine.

Voltage-gated Ca2+ currents are necessary for slow-wave propagation in the canine gastric antrum.

Electrical slow waves determine the timing and force of peristaltic contractions in the stomach. Slow waves originate from a dominant pacemaker in the orad corpus and propagate actively around and down the stomach to the pylorus. The mechanism of slow-wave propagation is controversial. We tested whether Ca(2+) entry via a voltage-dependent, dihydropyridine-resistant Ca(2+) conductance is necessary for active propagation in canine gastric antral muscles. Muscle strips cut parallel to the circular muscle were studied with intracellular electrophysiological techniques using a partitioned-chamber apparatus. Slow-wave upstroke velocity and plateau amplitude decreased from the greater to the lesser curvature, and this corresponded to a decrease in the density of interstitial cells of Cajal in the lesser curvature. Slow-wave propagation velocity between electrodes impaling cells in two regions of muscle and slow-wave upstroke and plateau were measured in response to experimental conditions that reduce the driving force for Ca(2+) entry or block voltage-dependent Ca(2+) currents. Nicardipine (0.1-1 microM) did not affect slow-wave upstroke or propagation velocities. Upstroke velocity, amplitude, and propagation velocity were reduced in a concentration-dependent manner by Ni(2+) (1-100 microM), mibefradil (10-30 microM), and reduced extracellular Ca(2+) (0.5-1.5 mM). Depolarization (by 10-15 mM K(+)) or hyperpolarization (10 microM pinacidil) also reduced upstroke and propagation velocities. The higher concentrations (or lowest Ca(2+)) of these drugs and ionic conditions tested blocked slow-wave propagation. Treatment with cyclopiazonic acid to empty Ca(2+) stores did not affect propagation. These experiments show that voltage-dependent Ca(2+) entry is obligatory for the upstroke phase of slow waves and active propagation.

Endogenous acyl ghrelin is involved in mediating spontaneous phase III-like contractions of the rat stomach.

In humans and dogs, it is known that motilin regulates phase III contractions of migrating motor complex (MMC) in the fasted state. In rats, however, motilin and its receptor have not been found, and administration of motilin failed to induce any phase III-like contractions. Ghrelin was discovered as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R) from the rat stomach. Ghrelin promotes gastric premature phase III (phase III-like contractions) in the fasted state in rats. We hypothesized that endogenous ghrelin regulates spontaneous phase III-like contractions in rats. Strain gauge transducer was sutured on the antrum and a catheter was inserted into the jugular vein. We studied the effects of i.v. administration of ghrelin and a GHS-R antagonist on gastric phase III-like contractions in conscious rats. Plasma level of ghrelin was measured by a radioimmunoassay. Ghrelin augmented spontaneous phase III-like contractions and a GHS-R antagonist significantly attenuated the occurrence of spontaneous phase III-like contractions. During the phase I period, plasma ghrelin level increased to its peak then returned to basal level, subsequently phase III-like contractions were observed. These results suggest that endogenous ghrelin regulates gastric phase III-like contractions in rats.

Epidural administration of morphine facilitates time of appearance of first gastric interdigestive migrating complex in dogs with paralytic ileus after open abdominal surgery.

Morphine is known to delay gastric emptying and intestinal transit, although epidural morphine is believed to decrease postoperative complications. However, these findings are still controversial and based only on clinical observations. We investigated the effects of epidural morphine administration on gut motility by measuring interdigestive migrating complex after open surgery in dogs. Twenty-eight beagles were divided into four groups (n = 7 each) to receive epidural saline (control group), epidural morphine, epidural ropivacaine, or low-dose continuous intravenous morphine. Strain gauge force transducers were sutured under open operation to the serosal surface of the stomach, duodenum, jejunum, and ileum to monitor gut motility. Time of appearance of first interdigestive migrating complex from the stomach propagated to the distal intestine was significantly shorter in the group that received epidural morphine compared with the other three groups. These results suggest that epidural administration of morphine may facilitate recovery from paralytic ileus after open abdominal surgery, perhaps through its effects on the central nervous system.

The effect of lidocaine on postoperative jejunal motility in normal horses.

OBJECTIVE: To measure the effect of lidocaine on the duration of the migrating myoelectric complex (MMC) and Phases I, II, and III of the MMC, spiking activity of the jejunum, and number of Phase III events when administered postoperatively to normal horses. STUDY DESIGN: Nonrandomized cross-over design. METHODS: Horses were anesthetized and via flank laparotomy 4 silver-silver chloride bipolar electrodes were sutured to the proximal jejunum. Electrical activity was recorded for 6 hours during 3 recording sessions beginning 24, 48, and 72 hours postoperatively. Saline (0.9% NaCl) solution was administered for 3 hours followed by lidocaine administration for 3 hours (1.3 mg/kg bolus intravenously [IV], 0.05 mg/kg/min IV constant rate infusion). RESULTS: Duration of MMC was unchanged during lidocaine administration (77 minutes-saline versus 105 minutes-lidocaine, P=.16). Durations of Phase I and II were unchanged during lidocaine administration (P=.19 and .056, respectively). Phase III was shorter during lidocaine administration (P=.002). Spiking activity was unchanged at all time periods during lidocaine administration (24 hours-P=.10; 48 hours-P=.95; and 72 hours-P=.12). The number of Phase III events was unchanged over all time periods during lidocaine administration (P=.053). CONCLUSIONS: Duration of MMC, spiking activity, and number of Phase III events was unchanged during lidocaine administration. CLINICAL RELEVANCE: Use of lidocaine as a prokinetic agent cannot be supported by this study in normal horses; however, results may differ in clinically affected horses.

Effects of ghrelin on feeding regulation and interdigestive migrating complex in rats.

OBJECTIVE: Ghrelin is an orexigenic peptide with remarkable prokinetic effects. However, its mechanisms in regulating feeding and gastrointestinal migrating myoelectrical complex (MMC) are not fully understood. The aim of this study was to examine the effects of ghrelin on feeding regulation and duodenal motility in rats. MATERIAL AND METHODS: Feeding regulation was investigated at different times after intravenous injection of ghrelin and its receptor antagonist (D-Lys3)GHRP-6 in fasted rats. Rats were supplied with a pair of silver bipolar electrodes embedded in the duodenal serosa for electromyography. Ghrelin was injected intravenously into the rats during the fed state or fasted state. Some rats were pretreated with atropine, phentolamine, propranolol, L-arginine, the 5-hydroxytryptamine3 receptor antagonist ondansetron, and (D-Lys3)GHRP-6. RESULTS: Ghrelin had little effect on food intake in the first 30 min after administration, but was found to increase feeding during the subsequent hours. (D-Lys3)GHRP-6 decreased feeding and antagonized the effect of ghrelin. Ghrelin induced duodenal MMC after administration in the fed state, and shortened the duodenal MMC cycle length and the duration of phase III during fasting. The amplitude and frequency of phase III were increased without affecting the percentage of phase III in the MMC cycle. Pretreatment with atropine, L-arginine, ondansetron, and (D-Lys3)GHRP-6 inhibited the effects of ghrelin. Propranolol and phentolamine had little influence on these effects. CONCLUSIONS: Ghrelin appears to be closely related to feeding and intestinal motility. The excitatory effects of ghrelin are dependent on the cholinergic pathway, and it has a close relationship with the NOS-NO or 5-HT pathway. The ghrelin receptor is involved in its activities.

Development of colonic motility in the neonatal mouse-studies using spatiotemporal maps.

Colonic migrating motor complexes (CMMCs) are spontaneous, anally propagating constrictions, repeating every 3-5 min in mouse colon in vitro. They are regulated by the enteric nervous system and may be equivalent to mass movement contractions. We examined postnatal development of CMMCs and circular muscle innervation to gain insight into mechanisms regulating transit in the maturing colon. Video recordings of mouse colon in vitro were used to construct spatiotemporal maps of spontaneous contractile patterns. Development of nitric oxide synthase (NOS) and cholinergic nerve terminals in the circular muscle was examined immunohistochemically. In adults, CMMCs appeared regularly at 4.6 +/- 0.9-min intervals (n = 5). These intervals were reduced by inhibition of NOS (2.7 +/- 0.2 min; n = 5; P < 0.05). CMMCs were abolished by tetrodotoxin (n = 4). CMMCs at postnatal day (P)10 were indistinguishable from adult. At birth and P4, CMMCs were absent. Instead, small constrictions that propagated both orally and anally, "ripples," were seen. Ripples were unaffected by tetrodotoxin or inhibition of NOS and were present in Ret(-/-) mice (which lack enteric neurons) at embryonic day 18.5. In P6 mice, only ripples were seen in control, but NOS inhibition induced CMMCs (n = 8). NOS terminals were abundant in the circular muscle at birth; cholinergic terminals were sparse but were common by P10. In mouse, myogenic ripples are the only mechanism available to produce colonic transit at birth. At P6, neural circuits that generate CMMCs are present but are inhibited by tonic activity of nitric oxide. Adult patterns appear by P10.

Peripheral mechanisms of intestinal dysmotility in rats with salsolinol induced experimental Parkinson's disease.

Gastrointestinal dysmotility in Parkinson's disease (PD) has been attributed in part to peripheral neurotoxine action. Our purpose was the evaluation of the salsolinol effect on intramuscular interstitial cells of Cajal (ICC), duodenal myoelectrical activity (DMA) and vagal afferent activity (VAA) in rats with experimental PD. Twenty rats were divided into 2 equal groups. Experimental PD was produced in one group by 3 weeks of the intraperitoneal salsolinol injections (50 mg/kg/day), whereas the 2-nd group served as control. DMA and VAA were recorded in both groups during fasting and stepwise--gastric distension (GD) of 10 ml. Subsequently fragments of duodenum were removed and intramuscular ICC were assessed as c-Kit antigen percentage in the duodenal muscular zone. Analyses of the fasting DMA and VAA recordings didn't reveal differences between the compared groups. During GD increase of DMA dominant frequency (p=0.04) and VAA frequency (p<0.01) was observed in the controls whereas in the salsolinol group both parameters remained unchanged. Image analysis of duodenum revealed decreased c-Kit expression in the salsolinol-injected animals (p=0.05). The results of our study may suggest the direct effect of salsolinol on both ICC and neuronal pathways of gastro-duodenal reflexes.

Effect of NO synthesis blocker on electrical activity of rat stomach and small intestine in the early postoperation period.

The effect of NO on electrical activity of the stomach and small intestine was studied in chronic experiments on rats during the early postoperation period. Generation of migrating myoelectric complex in the stomach and small intestine was impaired after abdominal surgery. Administration of NO synthesis blocker suppressed the inhibitory influences, which potentiated generation of the myoelectric complex in the small intestine. Our results suggest that NO is involved in the regulation of the migrating myoelectric complex in the small intestine during postoperation motor disturbances in the gastrointestinal tract.

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

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