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PubMed1997

A novel motility effect of tachykinins in normal and inflamed colon.

The role of tachykinins in stimulating phasic and giant migrating contractions (GMCs) in the normal and inflamed colon in conscious dogs was investigated by close-intra-arterial infusions of test substances. At low doses (0.1 nmol), substance P and neurokinin (NK1) receptor agonist ([Sar9,Met(O2)11]substance P] stimulated phasic contractions only. At higher doses (2.0 nmol), they stimulated phasic contractions and GMCs. The phasic contractions were blocked partially but significantly by prior close-intra-arterial infusions of tetrodotoxin and atropine but not by hexamethonium. NK1 receptor antagonist partially but significantly inhibited the phasic contractile response to substance P, whereas NK2 and NK3 receptor antagonists had no significant effect. The contractile response to NK2 receptor agonist was less than one-half of the response to substance P; NK3 receptor agonist did not stimulate any contractile activity. The stimulation of GMCs by higher doses of substance P was not blocked by prior infusions of atropine, tetrodotoxin, or NK1, NK2, and NK3 receptor antagonists, nor was the contractile response to substance P blocked by H1 and H2 receptor antagonists. Inflammation depressed the phasic contractile response but enhanced the stimulation of GMCs by substance P. The ability of substance P to stimulate GMCs is novel and suggests its potential role in increasing the frequency of these contractions during colonic inflammation.

Animals↗

PubMed2006

Circulating ghrelin levels after food intake during different phases of the migrating motor complex in man.

BACKGROUND: The timing of the migrating motor complexes (MMC) at food intake may influence gastric emptying and release of regulatory hormones. This report studies the relationships between phases I (motor quiescence) and II (intermediate frequency contractions) of MMC and prandial gut hormone response. MATERIALS AND METHODS: Seven fasting volunteers ingested a meal during phase I or II of MMC verified by manometry, using paracetamol as a marker for gastric emptying. Blood was sampled before, during and 210 min after food intake for analysis of ghrelin, motilin, insulin and paracetamol. RESULTS: The basal level of ghrelin during phase I was 127.5 +/- 25.4 pmol L(-1) and during phase II was 132.4 +/- 24.8 pmol L(-1). After food intake during phase I, ghrelin fell to 77.2 +/- 10 pmol L(-1); in phase II it fell to 82.7 +/- 17.8 pmol L(-1) within 60 min and returned to baseline levels after 120 min. Baseline levels of motilin were 16 +/- 2 pmol L(-1) and 18 +/- 3 pmol L(-1) during phases I and II, respectively. After food, motilin decreased to 8.5 +/- 0.7 pmol L(-1) and 8.7 +/- 1.0 pmol L(-1) within 60 min and returned to baseline after 90 min. Insulin levels in phases I and II were 8.1 +/- 1.2 mU L(-1) and 8.6 +/- 0.7 mU L(-1), respectively, reaching 138.9 +/- 35.6 mU L(-1) and 167.4 +/- 30.0 mU L(-1) at 45 min postprandially. CONCLUSIONS: The nutritional status of the gastrointestinal tract at food intake had only a limited impact on plasma ghrelin. After food intake, plasma ghrelin drops, similar to motilin, and resumes preprandial levels within 120 min.

Acetaminophen↗

PubMed1995

Effects of insulin and beta-adrenergic blockade on the migrating motor complex in humans.

BACKGROUND: Interdigestive small-intestinal motility is suppressed by hyperglycemia and also by hyperinsulinemia per se. Since hyperinsulinemia may increase sympathetic activity, the present study was undertaken to ascertain to what extent insulin affects phase III of the migrating motor complex (MMC) and MMC-related duodenal retroperistalsis and whether beta-adrenergic receptors may mediate the effects of insulin. METHODS: Fasting motility was studied in eight healthy volunteers on three occasions with an eight-lumen perfused pressure catheter, with closely spaced recording points in the proximal duodenum. On the control day 5-h antroduodenojejunal manometry was performed. On another study day euglycemic hyperinsulinemic clamping was performed for 2 h after an initial basal recording. On a 3rd day motility was recorded during propranolol infusion, combined with a period of euglycemic hyperinsulinemia. RESULTS: During hyperinsulinemia complete absence of phase III of the MMC in the gastric antrum was observed, whereas 55% of the MMC had a gastric phase-III component on the control day. The duration of phase III in the proximal duodenum was decreased during hyperinsulinemia compared with the control period (p < 0.05). This inhibitory effect of insulin on the activity front was not prevented by beta blockade. Under control conditions the proportion of retroperistaltic pressure waves in the proximal duodenum was 13 +/- 8% in early phase III, increasing in late phase III to 79 +/- 15% (p < 0.01). Duodenal phase III during hyperinsulinemia showed a similar increase in retroperistalsis, from 4 +/- 4% in early phase III to 67 +/- 21% in late phase III (p < 0.01). The corresponding proportions during beta blockade were 16 +/- 10% and 86 +/- 14%, respectively. CONCLUSIONS: Hyperinsulinemia per se abolishes antral phase III and makes the duodenal phase III shorter but does not interrupt the distinct pattern of retroperistalsis in late phase III. Beta-adrenergic receptors seem not to be important for these effects of insulin or for the retroperistalsis in duodenal phase III.

Adult↗

PubMed1996

Gastric antrectomy with selective gastric vagotomy does not influence gallbladder motility during interdigestive and postprandial periods.

Fasting gastrointestinal motility and gallbladder motility during the interdigestive state and in the postprandial period was studied in eight patients who were operated for ulcer disease with an antrectomy and selective gastric vagotomy. Nocturnal motility recording revealed all three phases of the migrating motor complex (MMC) in all but one patient, where no phase III activity was recorded. In the rest of the patients 3-10 events with phase III activity were recorded. At scintigraphy ([75Se]HCAT) a cyclic gallbladder filling and emptying in relation to the MMC cycle was found. Episodes with emptying were confined to phase II and a total of 13 episodes with a median duration of 25 min (range 10-70 min) were observed. A median of 10.7% (6.1-17.7%) of the gallbladder contents was emptied. In a control group of eight healthy young men the values were 13.5 min (9-36 min) and 6.9% (3.7-31.1%), respectively. These differences were not significant. During the postprandial period, a lag period in gallbladder emptying of median 15 min (5-20 min) was observed when food ingestion took place during phase I of the MMC. Thereafter a gradual emptying occurred with a rate of 0.95% min (0.71-1.15%/min). In a control group of healthy young males, the lag period was 13.5 min (9-22.5 min) and the emptying rate 0.61%/min (0.08-0.77%/min). When food ingestion occurred during phase II of the MMC, the lag period of gallbladder emptying in the patient group was median 0 min (0-5 min) and the emptying rate was 0.77%/min (0.33-0.86%/min). The values in the control group were 0 min (-9 to 13.5 min) and 0.76%/min (0.54-2.25%/min), respectively. These differences between the patients and controls were not significant. In conclusion, antrectomy and selective gastric vagotomy do not influence fasting gastrointestinal motility or gallbladder motility during the interdigestive state or in the postprandial period.

Aged↗

PubMed1993

Nitric oxide regulates migrating motor complex cycling and its postprandial disruption.

We investigated the role of nitric oxide (NO) in the regulation of migrating motor complex (MMC) cycling during the fasting state and its postprandial disruption. Intravenous infusion of N omega-nitro-L-arginine methyl ester (L-NAME) first produced a premature MMC and then disrupted MMC cycling for the rest of the day. The cycle length of the MMCs was significantly shorter than the control on the 2nd, 3rd, and 4th day after L-NAME infusion. The gastric cyclic motor activity (CMA) did not usually exhibit a premature cycle on the day of L-NAME infusion but was disrupted by L-NAME infusion; the duration of CMA disruption in the stomach was significantly longer than that of MMC disruption in the small intestine. Infusion of N omega-nitro-L-arginine (L-NNA) exhibited similar effects. The intravenous infusion of L-NAME also significantly shortened the duration of MMC disruption by a meal. L-Arginine alone had no significant effect on gastrointestinal motor activity during the fasting or the fed state, but when infused with L-NAME, it blocked the effects of NO synthase inhibition. Angiotensin II increased the mean arterial pressure to a level similar to that produced by L-NAME but had no significant effect on the fasting or the fed pattern of gastrointestinal motor activity. We conclude that NO containing nonadrenergic noncholinergic (NANC) neurons play a significant role in regulating MMC and CMA cycling during the fasting state and their disruption by a meal. However, NO may not be the only NANC neurotransmitter to inhibit contractions in the gut; phase I activity in the small intestine persisted during NO synthase inhibition by L-NAME or L-NNA.

Amino Acid Oxidoreductases↗

PubMed1998

[Regulatory role of 5-hydroxytryptamine and motilin in migrating motor complex of small bowel in dogs].

Migrating motor complex (MMC) was recorded by chronically implanted strain gauge transducers on the serosa of small bowel in conscious dogs. Two silastic catheters for injecting drugs and taking blood samples were put respectively in a vena jugularis externa and in a jejunal artery which perfused a 10-15 cm intestinal segment. The present study was undertaken to observe the effect of drugs administered intravenously and intraarterially on MMC and alterations of plasma 5-hydroxytryptamine (5-HT) and motilin in different phases of MMC. The results showed: (1) Levels of plasma 5-HT and motilin showed cyclical fluctuations in different phases of MMC, and 5-HT reached peak before peak of motilin. Plasma 5-HT level reached a peak [(41.2 +/- 1.3) ng/ml] in the later period of phase II, which increased significantly as compared with phase I [(22.4 +/- 1.1) ng/ml] (P < 0.01), but plasma motilin level had a peak [(580.0 +/- 30.2) pg/ml] in phase III of MMC, which was higher than that in phase I [(140.0 +/- 21.0) pg/ml] (P < 0.01). (2) Intravenous motilin and intraarterial 5-HT and motilin could induce phase III contraction in the canine proximal small bowel and in the perfused segment respectively. Amplitude of contractions caused by motilin was higher than that by 5-HT in the perfused segment. (3) 5-HT receptor antagonist, motilin antiserum, 5,6-dihydroxytryptamine and tetrodotoxin perfused intra-arterially inhibited expression of MMC in the perfused segment and its caudal propagation. We conclude that plasma 5-HT and motilin may be dominant factors which initiate MMC of canine small bowel, and 5-HT peak appears before peak of motilin. 5-HT neurons and motilin neurons in enteric nervous system may play an important role in controlling MMC of canine small bowel.

Animals↗

PubMed1994

Altered motility causes the early gastrointestinal toxicity of irradiation.

PURPOSE: Total abdominal radiation produces symptoms of nausea, vomiting abdominal cramping and diarrhea. Each of these symptoms is associated with disordered intestinal motility. This article reviews studies of large and small intestinal contractile activity following radiation exposure. METHODS AND MATERIALS: Studies of motility utilize strain gauge transducers surgically implanted on the seromuscular layer of the small intestine. All studies were performed in mixed breed dogs to record the occurrence of normal contractions, giant migrating contractions (GMCs) and retrograde giant contractions (RGCs) before, during and after irradiation (22.5 Gy in 9 fractions at 3 fractions/week). Giant migrating contractions and retrograde giant contractions are infrequent in the healthy state. However, in diseased states, GMCs are associated with abdominal cramps and diarrhea, and RGCs precede vomiting. RESULTS: In fasted animals, fractionated abdominal irradiation dramatically increased the frequency of GMCs, with the incidence peaking after the second dose. The increased frequency of GMCS occurred as early as a few hours after the first radiation fraction, and returned to normal within days of cessation of radiation. RGCs were also significantly increased after abdominal irradiation. The frequency of RGCs was greatest on the first and sixth dose of radiation. Clinically, the dogs developed nausea, vomiting and diarrhea as early as the first day of irradiation. In dogs studied in the fed state, decreased amplitude, duration, and frequency of postprandial contractions occurred. These changes may slow intestinal transit during irradiation. Radiation also produced a striking increase in the frequency of colonic GMCs; these changes in colonic motor activity were associated with diarrhea as early as the second irradiation. CONCLUSION: Changes in GI motility during fractionated irradiation precede the appearance of histopathological lesions in the GI tract. Thus, the symptoms of nausea, vomiting, and diarrhea experienced during radiotherapy (particularly those within the first week) are directly related to changes in bowel motility. It is hoped that further understanding of the etiology of these distressing symptoms will help to guide their treatment.

Animals↗

PubMed1998

Effect of octreotide on gastric and small bowel motility in patients with gastroparesis.

BACKGROUND: Octreotide has been shown to have effects on gastric and small bowel motility with implications for its role in treating patients with upper gastrointestinal dysmotility syndromes. Our aim was to investigate the effect of octreotide on antral and small bowel motility in patients with gastroparesis. METHODS: Upper gastrointestinal manometry was carried out continuously for a period of 30 h in 11 patients with gastroparesis. The spontaneous migrating motor complex (MMC) in the fasting state and octreotide-induced MMCs were characterized and compared with regard to site of origin, duration of phase III, amplitude of phase III and propagation velocity of the MMC along the gut. The 2-h postprandial motility index was compared after a control meal as well as after a 100 microg octreotide administration. RESULTS: In all 11 gastroparetic patients, octreotide induced a phase III-like activity front within minutes after administration and this primarily originated in the small bowel (86% of activity fronts compared with 32% of fronts originating in the small bowel prior to octreotide administration (P < 0.004)). Gastric initiation of these activity fronts dramatically decreased after octreotide administration, occurring in 68% of activity fronts prior to octreotide administration and 14% of occasions after octreotide injection (P < 0.05). The postprandial antral motility index was markedly reduced after octreotide administration (11.33 +/- 0.39 vs. 7.96 +/- 0.76, P < 0.0003) and octreotide re-established a motility pattern during the postprandial period that was similar to that normally seen in the interdigestive state. The octreotide-induced phase III activity fronts appeared at a higher frequency and had a higher propagative velocity compared to the spontaneous phase III fronts in the fasting state (9.27 +/- 0.82 vs. 5.56 +/- 0.81 cm/min, P < 0.05). CONCLUSIONS: We conclude that octreotide's marked inhibitory effect on antral contractility may serve to worsen clinical symptoms in patients with gastroparesis and therefore this agent should not be given in the periprandial period. Those gastroparetic patients with associated small bowel dysmotility and diarrhoea from bacterial overgrowth may benefit from the nocturnal administration of octreotide because of its stimulatory effect of phase III MMC activity as well as its known inhibitory effect on small bowel secretions.

Adult↗

PubMed2006

Duodenal interdigestive migrating motor complex in patients 5 years or more after pylorus-preserving gastrectomy for early gastric cancer.

BACKGROUND: We investigated the relationship between interdigestive migrating motor complex, phase III (IMMC-pIII) and postoperative quality of life (QOL) in pylorus-preserving gastrectomy (PPG) patients. MATERIALS AND METHODS: A total of 40 patients (26 men and 14 women; average age 59.4 years) 5 to 7.5 years after PPG for early gastric cancer (Billroth I) (average 6 years and 3 months) were divided into two groups according to the occurrence of IMMC-pIII from the duodenum, and their postoperative quality of life (QOL) was compared. RESULTS: As for appetite, "No change compared with before operation" was significantly more frequent in the IMMC-pIII positive group compared with the negative group (P=0.0002). Food consumption per meal compared with normal; "80% or more" was significantly more frequent in the IMMC-pIII positive group than the negative group (P=0.0002). Body weight loss during 5 years after surgery; "6 kg or more" was significantly more frequent in the IMMC-pIII negative group than the positive group (P=0.0002). Early dumping symptoms did not occur in any patients of either group. Reflux esophagitis and nausea; no patients in the IMMC-pIII positive group experienced these symptoms, which was significantly different from the negative group (P=0.0018). Abdominal pain occurred but was significantly less frequent in the IMMC-pIII positive group than in the negative group (P=0.0023). Epigastric fullness occurred but was less frequent in the IMMC-pIII positive group compared with the negative group (P<0.0001). Gastric stasis of the remnant stomach was significantly more frequent in the IMMC-pIII negative group than in the positive group (P<0.0001). Gholelithiasis was significantly more frequent in the IMMC-pIII negative group than in the positive group (P=0.0119). CONCLUSIONS: These results showed more satisfactory QOL in the IMMC-PIII positive group than in the negative group.

Duodenum↗

PubMed1999

The variability of the incremental postprandial portal vein flow response is partly caused by a relationship between fasting flow rate and phase activity of the migrating motor complex.

OBJECTIVE: Results from studies on portal flow rate (PFR) have demonstrated a considerable intra- as well as interindividual variability of the incremental integrated response (IIR). We hypothesized that part of the variation of the IIR might be related to variability of the fasting PFR caused by a relationship between PFR and characteristics of the migrating motor complex (MMC). DESIGN: We examined 12 healthy men and PFR was recorded by using the percutaneous colour Doppler technique. Gastric emptying (GE) was determined by scintigraphy and the meal consisted of an omelette of 100 g (1400 kJ; 60% fat, 20% protein, 20% carbohydrates) tagged with 99mTc sulphur colloids followed by 150 ml water mixed with 111In DTPA. The design included recording of PFR in phase II as well as in phase III of the MMC. Meal ingestion took place in the following duodenal phase I. Postprandial recordings of GE and PFR were performed at 10 min intervals for the following 2 h. RESULTS: Median (95% confidence limits) amount of solid emptied at 120 min was 68% (59-81%). PFR in phase III was significantly higher than in phase II (1.56 l/min (1.35-1.93 l/min) vs 0.96 l/min (0.84-1.12 l/min), P< 0.001). PFR increased after the meal and a peak flow of 2.19 l/min (1.58-2.46 I/min) was recorded 10 min after ingestion (P< 0.01 vs phase III). Based on these characteristics a difference in IIR is to be expected, and the calculations revealed that IIR is considerably higher in the phase II series than in the phase III series (50 l/min x 120 min (8-90 l/min) vs -26 l/min x 120 min (-55 to 1 l/min), P< 0.001). In both series a weak but significant inverse relationship was demonstrated between amounts emptied during a 20-min period and the corresponding IIR (n = 72; r = -0.27, P< 0.05 (III); r = -0.29; P< 0.05 (II)). CONCLUSION: We conclude that fasting PFR is related to phase activity of the MMC and characteristics of the postprandial IIR depend upon MMC activity at the time of recording of the fasting value. Future studies on PFR need to be performed with phase related recording of fasting flow and meal ingestion in relation to preselected characteristics of the MMC.

Adult↗

PubMed2000

Human postprandial gastric emptying of indigestible solids can occur unrelated to antral phase III.

According to animal experiments, postprandial gastric emptying of indigestible solids is mainly related to the antral phase III activity of the migrating motor complex. Gastric emptying of indigestible solids in humans has not been directly correlated to pressure recordings. The aim of the present study was to investigate the postprandial emptying pattern of indigestible solids in humans and its relation to fed and fasted antral motility. Ten healthy volunteers participated. After an overnight fast they had a standard breakfast. Two sizes of radiopaque markers (ROMs) were given with the test meal; ten cubes each of side measurement 1.5 mm and 3 mm, respectively. Emptying of the ROMs from the stomach was followed by fluoroscopy with simultaneous antral manometry. In six of the subjects, fasting antral manometry was performed on one day and on another day, the emptying of 7 mm cylindrical particles together with 3 mm cubes, in the absence of a gastric tube was recorded. All ROMs were emptied within 5 h (range 1.5-4.5 h). In all subjects, the smaller particles (1.5 mm) showed a slight, insignificant tendency to move from the stomach more rapidly than the larger (3 mm) particles. None of the subjects had an antral phase III before all ROMs were emptied from the stomach. Instead, the typical irregular postprandial pressure activity was present in all subjects until the emptying was completed. Furthermore, the highest postprandial motility index during the emptying study was far below the motility index during phase III, but comparable to the motility index during late phase II. Emptying of the 7 mm particles occurred significantly more slowly at 1.5-2.5 h, but otherwise was similar to the emptying of the smaller particles. There was no difference between emptying of the 3 mm cubes with or without the presence of the tube. Contrary to common opinion, gastric emptying of indigestible solids after a meal can occur unrelated to the antral phase III, at least up to a particle size of 3 mm and perhaps even 7 mm. These findings are of great importance for the evaluation of gastric emptying of indigestible solids, including the pharmacodynamics of orally administered drugs.

Adult↗

PubMed1995

Comparison between physiologic and erythromycin-induced interdigestive motility.

BACKGROUND: The last part of duodenal phase III of the migrating motor complex behaves as a retroperistaltic pump. We have compared the phase-III-like gastroduodenojejunal activity induced by erythromycin with the naturally occurring phase III, focusing on peristaltic patterns. The effect of two doses of erythromycin, 3 mg/kg/h and 12 mg/kg/h (in four subjects), or saline, given intravenously for 15 min, was studied in nine fasting healthy subjects (five men and four women). METHODS: Motility was recorded on three different days. On one day standard 5-h eight-channel antroduodenojejunal manometry was performed and saline infused 30 min after the first phase III. On the other two study days, erythromycin in the low or the high dose was infused and recording performed for another 2-h period. RESULTS: The low dose of erythromycin induced a phase III in the stomach in all subjects within 12.8 +/- 1.4 min. In contrast, the higher dose did not induce phase-III activity within the 1st h after infusion but induced marked antral pressure waves. The duration of the erythromycin-induced phase III and the naturally occurring antral phase III was 4.7 +/- 1.7 and 1.9 +/- 0.3 min, respectively (p < 0.01). The duration of the erythromycin-induced phase III in the proximal jejunum was 44% shorter than the spontaneous one (p < 0.01). The propagation velocity, from the proximal duodenum to the proximal jejunum, of the erythromycin-induced phase III was slower than that of the spontaneous phase III: 5.7 +/- 0.9 and 15.9 +/- 3.9 cm/min, respectively (p < 0.01). In the proximal duodenum the proportion of retrograde pressure waves (of all propagating waves) was about 10% in early phase III, increasing to about 85% in late phase III in both the spontaneous and erythromycin-induced phase III. In the proximal jejunum retrograde pressure waves were not observed in phase III. CONCLUSIONS: Erythromycin given in a low dose is very effective in inducing phase-III-like motility. The last part of duodenal phase III is characterized by retroperistalsis also when this motility phase is induced by erythromycin.

Adult↗

PubMed1995

Increases in plasma motilin follow each episode of gallbladder emptying during the interdigestive period, and changes in serum bile acid concentration correlate to plasma motilin.

BACKGROUND: The relationship between each single period of gallbladder emptying during the migrating motor complex (MMC) cycle and changes in concentration of plasma motilin and serum bile acids is unknown. METHODS: The variations in the concentration of plasma motilin and serum bile acids in relation to interdigestive gallbladder motility and the MMCs was studied in nine healthy male volunteers. A method combining biliary scintigraphy (99mTc-labelled dimethyl-iminodiacetic acid) and continuous pressure recording from the antroduodenal region was used. RESULTS: During 9 MMC cycles a total of 15 episodes of gallbladder emptying were observed with a median (range) duration of 25 min (15-45 min). Each episode of gallbladder emptying was followed by a steep increase in plasma motilin, reaching a median value of 30 pmol/l (13-43 pmol/l), corresponding to an increase of 18 pmol/l (4-33 pmol/l). The increase in plasma motilin started at the beginning of gallbladder emptying, but the peak value was not reached until a median of 20 min (10-45 min) later. Low plasma motilin concentrations were found between the emptying periods in cases with two or more emptying during the MMC cycle. The serum concentration of bile acids also showed a cyclic variation in relation to gallbladder motility. During periods of gallbladder emptying serum bile acid concentration had a median value of 1.78 mumol/l, as compared with a median value of 1.17 mumol/l during periods of gallbladder filling. This difference did not reach significance, however. In the pooled data from all subjects, a significant correlation (p < 0.01) between the serum concentration of bile acids and plasma concentration of motilin was found. CONCLUSION: Gallbladder emptying was followed by a steep increase in plasma motilin concentration, and in cases of two or more emptying periods during the MMC cycle the concentration decreased in between. The shape of the serum bile acid profile is dependent on the intestinal transport and absorption of bile acids, and the significance of the cyclic variation in serum concentration of bile acids in relation to plasma motilin, gallbladder motility, and MMC needs further investigation.

Adult↗

PubMed2006

Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain.

We investigated whether strong compression of an intestinal segment by giant migrating contractions (GMCs) initiates pseudoaffective signals from the gut, similar to those initiated by its distension with a balloon. The experiments were performed on conscious dogs by using close intra-arterial infusions of test substances that affect the receptors only in the infused segment. The stimulation of GMCs by close intra-arterial infusion of CGRP or distension of an intestinal segment by balloon increased the heart rate; the increase in heart rate was greater when the balloon distension and GMCs occurred concurrently in separate intestinal segments. The suppression of contractility in the distended segment blocked the increase in heart rate. By contrast, the stimulation of rhythmic phasic contractions (RPCs) or their spontaneous occurrence did not increase the heart rate. The occurrence of GMCs as well as intestinal distension also produced descending inhibition. The descending inhibition was blocked by the inhibition of nitric oxide synthase, but it was unaffected by the inhibition of adenylyl cyclase, purinergic receptors P2X and P2Y, and muscarinic receptors M(1) and M(2). The synaptic transmission for descending inhibition was mediated primarily by nicotinic receptors and activation of nitric oxide synthase. It was unaffected by the inhibition of tachykinin receptors NK(1), NK(2), and NK(3); serotonin receptors 5-HT(1A), 5-HT(2)/5-HT(1C), 5-HT(3), and 5-HT(4); and muscarinic receptors. Our findings show that GMCs, but not RPCs, initiate pseudoaffective signals from the gut. In the presence of visceral hypersensitivity or impaired descending inhibition, the GMCs may become a noxious stimulus.

Afferent Pathways↗

PubMed1998

Independent cycles of exocrine pancreatic secretion, hormones and gastroduodenal motility in healthy fasting humans: reassessment of a complex partnership.

BACKGROUND: Interdigestive pancreatic secretion cycles in close association with the phases of the migrating motor complex (MMC) and release of regulatory hormones. The extrinsically denervated pancreas exhibits an intrinsic cyclic rhythm. We hypothesized that this intrinsic rhythm is normally present in the intact human pancreas. METHODS: 19 healthy males (age range 26-35 years) were studied after 12 h fasting. A manometry catheter was positioned with four pressure ports in the antrum and three in the duodenum, and motility was recorded for a complete MMC cycle or 5 h. Duodenal aspirates were sampled at 15-min intervals, and immediately analysed for amylase, lipase and chymotrypsin activities; enzyme outputs were calculated by standard marker perfusion techniques. Plasma levels of pancreatic polypeptide (PP) and motilin were also determined (RIA) at 15-min intervals. RESULTS: Output of amylase, lipase and chymotrypsin occurred in parallel. All phase III motility fronts were accompanied by a pancreatic secretory peak. However, in 12 subjects at least one secretory peak was observed without the concomitant occurrence of phase III. A total of 16 out of 51 secretory peaks identified across all subjects were independent (31%). These phase III-independent peaks of pancreatic secretion occurred in subjects with a longer MMC cycle (160 +/- 19 min vs 102 +/- 13 min, P < 0.05). Phase III-associated and -independent peaks had a similar magnitude (amylase output: 21.6 +/- 3.9 kUh-1 vs 21.1 +/- 2.8 kUh-1, respectively). Irrespective of MMC phases, antral but not duodenal motor activity was closely correlated with fluctuations of pancreatic secretion (P < 0.05). Cycling of PP and motilin were also closely coordinated with pancreatic enzymes, with a particularly tight link between endocrine and exocrine secretion from the pancreas. CONCLUSIONS: Peaks of pancreatic secretion invariably occur when a phase III motor activity occurs, but additional secretory peaks occur without a concomitant phase III. Interdigestive phasic pancreatic secretion is tightly coordinated with PP and motilin release as well as with antral motor activity. An intrinsic rhythm of the pancreas distinct from other cyclic activity may be present in healthy humans, expressed as peaks of pancreatic secretion independent of a motor phase III.

Adult↗

PubMed2003

A smooth muscle tone-dependent stretch-activated migrating motor pattern in isolated guinea-pig distal colon.

We have investigated the tone dependence of the intrinsic nervous activity generated by localized wall distension in isolated segments of guinea-pig distal colon using mechanical recordings and video imaging of wall movements. A segment of colon was threaded through two partitions, which divided the colon for pharmacological purposes into oral, stimulation and anal regions. An intraluminal balloon was located in the stimulation region between the two partitions (12 mm apart). Maintained colonic distension by an intraluminal balloon or an artificial faecal pellet held at a fixed location generated rhythmic (frequency 0.3 contractions min(-1); duration approximately 60 s) peristaltic waves of contraction. Video imaging of colonic wall movements or the selective application of pharmacological agents suggested that peristaltic waves originated just oral (< or = 4 mm) to the pellet and propagated both orally (approximately 11 mm s(-1)) and anally (approximately 1 mm s(-1)). Also, during a peristaltic wave the colon appears to passively shorten in front of a pellet, as a result of an active contraction of the longitudinal muscle oral to the pellet. Faecal pellet movement only occurred when a rhythmic peristaltic wave was generated. Rhythmic peristaltic waves were abolished in all regions by the smooth muscle relaxants isoproterenol (1 microM), nicardipine (1 microM) or papavarine (10 microM), and by the neural antagonists tetrodotoxin (TTX; 0.6 microM), hexamethonium (100 microM) or atropine (1 microM), when added selectively to the stimulation region. Nicardipine, atropine, TTX, or hexamethonium (100 microM) also blocked the evoked peristaltic waves when selectively added to the oral region. Nomega-nitro-L-arginine (L-NA; 100 microM) added to the anal region reduced the anal relaxation but increased the anal contraction, leading to an increase in the apparent conduction velocity of each peristaltic wave. In conclusion, maintained distension by a fixed artificial pellet generates propulsive, rhythmic peristaltic waves, whose enteric neural activity is critically dependent upon smooth muscle tone. These peristaltic waves usually originate just oral to the pellet, and their apparent conduction velocity is generated by activation of descending inhibitory nerve pathways.

Anesthetics, Local↗

PubMed2001

Study of the mechanism underlying the difference in motility between the large and small intestine: the "single" and "multiple" pacemaker theory.

The common movement of the small intestine (SI) is peristalsis and of the large intestine (LI) are giant migrating contractions. The mechanism underlying the difference in the type of motility between the SI and LI is yet to be elucidated; the current communication investigated this point. 7 pigs (4 male) were anesthetized, abdomen opened and a balloon-ended catheter was introduced into the right colon through ileotomy. Balloon was filled in increments of 10 ml of saline and the EMG activity of the colonic longitudinal and circular muscle layers was recorded before and after myotomy performed between 2 of the 3 electrodes fixed to the colon. The balloon was then withdrawn, located in the terminal ileum and distended in increments of 2 ml; the ileal EMG activity was registered before and after myotomy done between 2 of the 3 electrodes applied to the ileum. The LI showed slow waves or pacesetter potentials (PPs) and action potentials (APs) which had the same frequency, amplitude and conduction velocity from the 3 electrodes of the same animal. The waves were recorded from the longitudinal and not the circular muscle coat. Upon LI distension, the electric activity increased and was recorded also from the circular muscle. At 40-50 ml distension, the balloon was dispelled to the transverse colon. Electric activity from SI was similar to that of the LI, but was not the same from the 3 electrodes; it diminished aborally. It increased with increasing balloon distension until, at 8-10 ml distension, the balloon moved slowly aborally. Electric waves were recorded proximally but not distally to colonic myotomy, and the balloon moved up to the cut. In the SI, waves were recorded both proximally and distally to the ileal myotomy, and the balloon moved across the cut. The fact that the colonic electric waves displayed the same variables from the 3 electrodes and that they were not recorded distally to the colonic myotomy, would suggest the presence of a "single" colonic pacemaker, probably situated in the cecum. This is in contrast to the hypothesis of the "multiplicity" of the small intestinal pacemakers, which is based on the fact that the electric activity diminished as the waves propagated aborally and on the existence of slow waves distal to the ileal myotomy. The concept of "single" and "multiple" pacemakers explaining the difference in the motility of small from that of large gut needs further studies.

Animals↗

PubMed2000

Cytotoxic chemotherapy has minimal direct effect on gastric myoelectric activity in children with 5HT(3) antagonist prophylaxis.

BACKGROUND: Cancer patients receiving cytotoxic chemotherapy frequently develop nausea and vomiting. The direct effect of chemotherapy on gastric pacemaker is not clear. The objective of this study was to assess the direct interference of gastric electrical activity by chemotherapeutic agents as a possible cause of vomiting using electrogastrography (EGG). PROCEDURE: Fasting surface EGGs were recorded in 24 children with malignancy and 24 age-matched controls. All oncology patients received the intravenous prophylatic ondansetron. According to the known emetic potential of the medications they received, the children were divided into mild, moderate, and severe groups. The EGG recordings of oncology patients were segmented into prechemotherapy period, chemotherapy period, and emetic period. The EGG data from each period were collected and analyzed (paired t-test and Mann-Whitney U test). RESULTS: There were 24 children (M:F ratio: 14:10), with a mean age of 9.6 years. Eight children vomited during the course of recording (0/3 from the mild group, 2/6 from the moderate group, and 6/15 from the severe group). The average duration of intravenous medication infusion was 7.8 hr (range 2 min to 24 hr). There was no difference between the EGG of normal control and the prechemotherapy EGG of the oncology patients. No difference was detected between the EGG data from the prechemotherapy period and the chemotherapy period. A statistically significant increase in tachygastria was detected in emetic periods (28 episodes, mean duration 5 min; P = 0.01). CONCLUSIONS: Insignificant EGG changes during chemotherapy suggest that chemotherapy has a minimal direct effect on gastric pacemaker. Tachygastria seemed to be a secondary effect of vomiting rather than the cause of it. These preliminary findings suggest that efforts to modify gastric electrical rhythm as a means of management of chemotherapy-induced vomiting may be futile. Further studies to identify factors responsible for vomiting are warranted.

Adolescent↗