Distension-stimulated propagated contractions in human colon

To investigate the mechanisms for elicitation of peristaltic activity in the human colon, we studied the effect of balloon distension of the transverse, descending, and sigmoid colon and the rectum. Fifteen healthy subjects were studied by means of a colonoscopically positioned probe carrying a 5-cm latex balloon. After positioning of the probe, stepwise distension was performed for each colonic segment (transverse, descending, sigmoid, rectum), and the onset of large (>50 mm Hg) and small (<50 mm Hg) propagated waves was observed. Analysis of the tracings showed: (1) In 8/15 subjects (53.3%), balloon distension elicited propagated contractions, but these contractions were qualitatively different from the spontaneously occurring high-amplitude propagated contractions previously found to occur in association with defecation. Therefore, intraluminal distension is probably not the cause of defecation-associated high-amplitude propagated contractions. (2) Pain reports were poorly correlated with propagated contractions elicited by balloon distension, suggesting that these contractions are not the cause of the pain produced by balloon distension. (3) The transverse colon shows lower pressures, fewer pain reports, and fewer large propagated contractions in response to balloon distension as compared to the descending and the sigmoid colon.     

Physiology and pathophysiology of colonic motor activity

The basic motor function of the colon is to mix and knead its contents, propel them slowly in the caudad direction, hold them in the distal colon until defecation, and provide a strong propulsive force during defecation. Infrequently, it also produces mass movements in the proximal colon. These motor functions are achieved in most species by three different types of contractions: the individual phasic contractions that include the short- and long-duration contractions, organized groups of contractions that include the migrating and nonmigrating motor complexes, and special propulsive contractions (giant migrating contractions). The spatial and temporal patterns of all of these contractions are controlled by myogenic, neural, and chemical control mechanisms. The individual phasic contractions are highly disorganized in time and space in the colon. For this reason, they are effective in mixing and kneading and slow distal propulsion. The underlying cause of the disorganization of short duration contractions is the irregularity in the frequency and waveshape of colonic electrical control activity and its phase unlocking throughout the colon. The individual contractions in many species occur in cyclic bursts called contractile states. At least in some species, these contractile states exhibit mostly caudad and sometimes orad migration. However, there are also nonmigrating or randomly migrating contractile states in the colon. These two patterns of contractile states are called colonic migrating motor complexes and colonic nonmigrating motor complexes, respectively. The giant migrating contractions provide the strong propulsive force for defecation and mass movements. The neural control of colonic contractions is organized at three levels--enteric, autonomic, and central. The enteric nervous system contains cholinergic and peptidergic neurons and plays a major role in the control of colonic contractions. The autonomic nerves, the vagi, pelvic, lumbar colonic, hypogastric, and splanchnic nerves, seem to continuously monitor the state of the colon and provide a modulatory input when necessary. These nerves play a major role in the reflexive control of colonic motor function. The voluntary input from the central nervous system coordinates the motor activity of the colon, rectum, anal canal and sphincters for orderly evacuation of feces during defecation. The role of acetylcholine, nonadrenaline, and the yet to be completely identified nonadrenergic, noncholinergic neurotransmitter, possibly VIP, in the control of contractions is fairly well established. Besides these, there are several other peptides and chemicals that are localized in the colonic wall; their physiological roles remain unknown. Colonic motor activity has been studied in several disease states. The findings have not always been consistent.(ABSTRACT TRUNCATED AT 400 WORDS)     

Characterization of Propagating Contractions in Proximal Colon of Ambulatory Mini Pigs

The aim of this study was to characterizepropagating contractions in the unprepared colon offreely ambulating mini pigs. A telemetric method wasused to record colonic motility continuously for sixconsecutive days in a 40-cm segment of proximal colon.Propagating contractions occurred over a wide range ofpropagation rates (0.4-16.7 cm/sec), peak amplitudes(10-116 mm Hg) and pressure wave durations (5.3-40.0 sec). Propagating contractions were dividedinto two groups by duration and wave-form:short-duration symmetrical and long-durationasymmetrical. Short-duration (7.8 ± 0.9 sec)symmetrical wave-from propagating contractions exhibited a higher frequency (27.9± 2.6 events/day), more rapid propagation rate(3-16.7 cm/sec; mean SEM: 4.9 ± 1.7 cm/sec), anda lower peak amplitude (31.2 ± 0.9 mm Hg)compared to long-duration (19.2 ± 5.1 sec) asymmetricalpropagating contractions, which were less frequent (6.1± 0.7 events/day), slower in propagation rate(0.4-2 cm/sec; mean SEM: 1.5 ± 0.7 cm/sec), andhigher in peak amplitude (51.6 ± 2.4 mm Hg). Theresults show that propagating contractions occur over awide spectrum, from short-duration, low-amplitude,rapidly propagating contractions to longduration,high-amplitude, slowly propagating contractions.     

Long-term esophageal manometry in healthy subjects

Although long-term esophageal manometry is increasingly used in clinical practice, the normal values of contraction parameters are poorly defined. In addition, limited data are available on the effect of age on esophageal motility. Therefore, 44 healthy subjects (age range: 22–85 years) were investigated with a probe combining two pressure transducers 10 cm apart. All subjects were asked to follow their normal daily routine. The characteristics of contraction events (amplitude, duration) and type of propagation (propulsive, simultaneous) were analyzed for the total time and predefined periods: meal, daytime (interprandial), and supine. Equally high distal and proximal median pressure amplitudes (39.5 and 37 hPa) and durations (3.4 and 3.2 sec) were observed. The median percentages of propulsive and simultaneous waves were 56% and 10%. The individual contraction characteristics differed significantly in these three selected periods for most motility parameters: distal and proximal pressure amplitudes, distal duration, and propulsive contractions. To evaluate the influence of age on normal values, the subjects were divided into two age groups (median age: 28.5 and 62.4 years). In the elderly group the distal pressure amplitude, the distal duration, and the percentage of simultaneous waves increased, whereas the percentage of propulsive waves, the proximal pressure amplitude, and the proximal duration decreased. However, the differences observed were only minor and rarely reached the level of statistical significance (distal pressure amplitude and duration in the supine period). In conclusion, the physiological motor activity of the esophagus is characterized by significant diurnal variation. Furthermore the motility data are little influenced by age. Therefore, individual contraction characteristics should be considered in the analysis of motility data. Since age is of minor influence on esophageal motility, we believe that it is not required to create age-related control data for study populations of this size.     

Twenty-four hour recordings of colonic motility in patients with diverticular disease

INTRODUCTION: Diverticular disease of the colon is one of the most common pathologic entities in western countries. Although altered motility of the large bowel is commonly believed to be one of the major pathophysiologic mechanisms, no convincing evidence has been reported yet. In fact, only a few conflicting studies concerning distal colonic motility (with no information on forceful propulsive activity) are available in the literature. PURPOSE: The purpose of the present study was to investigate basal and stimulated (postprandial) colonic motility from the transverse (not affected), descending, and sigmoid colon in patients with diverticular disease, together with detection of high-amplitude propagated contractions (mass movements). Motility data from patients were compared with those obtained in healthy control subjects. METHODS: Ten patients and 16 control subjects of both sexes were recruited for the study. In all subjects, colonic motility was recorded for a 24-hour period by a colonoscopically positioned manometric catheter. Two 1000-kcal mixed meals were served during the study. RESULTS: Compared with control subjects, patients with diverticular disease displayed significantly increased amounts of motility in the affected segments; the response to a physiologic stimulus (meal) was also abnormal in the patients' group. Diverticular disease patients also had a significant increase of forceful propulsive activity compared with control subjects (average = 10.3±2.7/subject/day high-amplitude propagated contractions for patients and 5.5±0.8/subject/day for control subjects;P=0.051); interestingly, about 20 percent of such activity was abnormal, being propagated in a retrograde fashion. CONCLUSIONS: We concluded that patients with diverticular disease of the colon have abnormal motor and propulsive activities of the large bowel, which are confined to the affected segments.During the period this study was performed, Dr. Battaglia was on leave from the Department of Clinical Pathophysiology, University of Torino Medical School.     

Dopamine D1-Like Receptor Subtypes in the Rat Kidney: A Microanatomical Study

The microanatomical localization of dopamine D_1A and D_1B receptor subtypes was investigated in sections of rat kidney using immunohistochemicals techniques with anti-dopamine D_1A and D_1B receptor antibodies. Microanatomical analysis was limited to the various components of nephron. Dopamine D_1A receptor immunoreactivity was found primarily in the epithelium of loop of nephron (loop of Henle) and of collecting tubules. A less intense immunoreactivity was observed within proximal and distal convoluted tubules as well as in juxtaglomerular complex. Dopamine D_1B receptor immunoreactivity was found primarily in proximal and distal convoluted tubules and within the juxtaglomerular complex. A less intense immunoreactivity was observed in the epithelium of collecting tubules followed by the loop of nephron.

The demonstration of the localization of dopamine D_1A and D_1B receptor subtypes along the nephron may contribute to better define their significance in physiological and pathological conditions.     

Cooperative Roles of Colon and Anorectum During Spontaneous Defecation in Conscious Dogs

Colorectal motility during spontaneous defecation was investigated using force strain gauge transducers implanted in the proximal colon, distal colon, rectum, and anus in six dogs. One 24-hr recording and several defecation recordings were made in each dog. During 24-hr recordings, 29 giant contractions were observed in the distal colon. The giant contractions, which propagated to the rectum, accompanied evacuation more frequently than those that stopped at the distal colon (P < 0.05). Of 66 episodes of defecation, 63 (95%) were accompanied by a giant contraction of the distal colon. Of these, 57 (90%) propagated to the rectum. In three events, giant contraction originated at the rectum. The rectum relaxed prior to the contraction. The internal anal sphincter also relaxed. Migration of giant contraction to the rectum, rectal relaxation-contraction sequence and sphincter relaxation played important roles during defecation. Defecation is a consequence of successive phenomena occurring in both the colon and anorectum.     

Electrical impedance, a sensory system for detection of rectal filling after anorectal reconstruction

BACKGROUND: Total anorectal reconstruction with dynamic graciloplasty is an alternative to a permanent colostomy; however, perfect continence cannot be achieved because of loss of sensitivity. This study was designed in dogs to determine whether monitoring of rectal electric impedance can give information about fullness or motility of the rectum. METHODS: Four adult female beagle dogs underwent rectal electric impedance measurements using a bipolar electrode implanted on the rectal wall. An alternating current of 1 microA at a frequency of 4 kHz was applied between the two wires. Variations of impedance (called impedance waves), defecations, and weight of stools were recorded and analyzed. RESULTS: The basal rectal impedance was 682+/-19 omega. During the period of observation (n = 4), 84 impedance waves (amplitude, 72+/-2 omega; duration, 58+/-11 minutes) were observed and 33 defecations (weight of stools, 74+/-6 g) occurred. Four types of impedance waves were identified and classified into two groups: low-amplitude or short-duration waves (Types I, II, and III), and high-amplitude and long-duration waves (Type IV). Frequency of defecation was associated with the amplitude of the waves. The weight of stools was correlated with the duration of the waves (r = 0.574, n = 27, P = 0.002). Types I, II, and III waves were correlated with eventual partial defecations, whereas Type IV waves were correlated with complete defecations. After defecation, no spontaneous new defecation occurred before recovering at least 80 percent of the basal impedance. CONCLUSIONS: Rectal impedance variations are correlated with defecation in a canine model, and single bipolar measurements provide a suitable evaluation of rectum fullness. This suggests the possible use of impedance signals to control electrostimulated graciloplasty after anorectal reconstruction.     

Low-amplitude propagated contractile waves: a relevant propulsive mechanism of human colon

BACKGROUND: Human colonic motility is still poorly understood, especially as far as concerns its propulsive function. Available data refer almost exclusively to the forceful propulsive activity, which is recognized as high-amplitude propagated contractions, the manometric equivalent of mass movements. By contrast, information on less vigorous propulsive contractions is still lacking. AIMS: To investigate the presence and behaviour of low-amplitude propagated contractile waves (less than 50 mmHg in amplitude) in the colon of healthy humans during a 24-hour study period. SUBJECTS AND METHODS: A series of 16 healthy volunteers of both sexes entered the study, and were investigated by a standard technique involving a colonoscopically-positioned manometric catheter. During the study, two standard 1,000 kcal mixed meal and a 450 kcal breakfast were served. The recordings were, therefore, scanned for the presence of low-amplitude propagated contractile waves (waves of less than 50 mmHg in amplitude, propagated over at least three consecutive recording ports), their daily distribution, and their relationship with physiological events. RESULTS: Low-amplitude propagated contractile waves were constantly present in all the tracings, with an average of about 61 events/subject/day and a mean amplitude of about 20 mmHg. More than 80% of these events appeared during the day, with a significant (p<0.05) increase after meals and after morning awakening. In 25% of subjects, these waves were accompanied by emission of flatus. CONCLUSIONS: In the human colon, low-amplitude propagated contractile waves are a constant physiological propulsive pattern, which is generally related to sleep-wake cycles and meal ingestion.     

GR 38032F (Ondansetron), a selective 5HT3 receptor antagonist,slows colonic transit in healthy man

The newly recognized class of 5-hydroxytryptamine receptors (5HT₃) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT₃ receptors are present on enteric neurons, and 5HT₃ blockers may produce mild constipation; we thus hypothesized that 5HT₃ receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT₃ antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18–70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P<0.0005). Transit times through the left colon (P<0.0005) and rectosigmoid (P<0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P<0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug. We conclude that 5HT₃ receptors may be involved in the regulation of colonic transit in healthy man.Supported in part by a grant from Glaxo Group Research, Ltd., and the Mayo Digestive Disease Center (grant DK34988, National Institutes of Health, Bethesda, Maryland).Presented, in part, at the American Motility Socicty in October 1988, and published as an abstract inGastroenterology 95:891, 1988.     

Involvement of parasympathetic pelvic efferent pathway in psychological stress-induced defecation

AIM:To investigate the role of the pelvic nerve pathway in stress-induced acceleration of colorectal transit and defecation in rats.METHODS:Surgical transection of rectal nerves(rectal branches of the pelvic nerve),vagotomy(Vag) or adrenalectomy(Adx) were performed bilaterally in rats.Number of fecal pellet output of these rats was measured during 1-h water avoidance stress(WAS).To evaluate the colonic transit,rats were given phenol red through the catheter indwelled in the proximal colon and subjected to WAS.After WAS session,entire colon and rectum were isolated and distribution of phenol red was measured.Distal colonic and rectal transit was evaluated using glass bead.Rats were inserted the glass bead into the distal colon and evacuation rate of the bead was measured.Neural activation was assessed by immunohistochemical staining of c-Fos and PGP9.5 in colonic whole-mount preparations of longitudinal muscle myenteric plexus(LMMP).RESULTS:In the sham-operated rats(sham op),WAS significantly increased defecation and accelerated colorectal transit with marked elevation of plasma corticosterone level.Compared with sham-operated rats,increase in the excretion of fecal pellets during WAS was significantly reduced by rectal nerve transection(RNT)(sham op:6.9 ± 0.8 vs RNT:4.3 ± 0.6,P < 0.05) or Vag(sham op:6.4 ± 0.8 vs Vag:3.7 ± 1.1,P < 0.05),although corticosterone level remained elevated.Adx-rats significantly increased the defecation despite the lower corticosterone level.Distribution pattern of phenol red showed RNT inhibited distal colonic and rectal transit accelerated by WAS,while Vag inhibited proximal colonic transit.Suppression of distal colonic and rectal transit by RNT was further confirmed by the bead evacuation rate(sham op:80.0% vs RNT:53.8%).WAS significantly increased the number of c-Fos-immunoreactive neural cells in the LMMP of the proximal and distal colon,whereas c-Fos expression was decreased by RNT in the distal colon(sham op:9.0 ± 2.0 vs RNT:4.4 ± 1.0,P < 0.05) and decreased by V     

Motor responses of the oesophagus to intraluminal distension in normal subjects and patients with oesophageal clearance disorders.

Oesophageal motor responses to intraluminal distension were studied manometrically in 16 healthy volunteers and in nine patients with disordered swallowing, who had prolonged oesophageal clearance without structural abnormality. In the normal subjects distension was associated with an increased number of secondary contractions above the balloon, decrease of all contractile activity below the balloon and was accompanied by an aborally propulsive force which occurred independently of the perception of discomfort. Cholinergic blockade abolished the proximal distension induced contractile response, but did not affect primary peristalsis. Despite normal sensory thresholds, proximal excitatory responses to distension were absent in six and distal inhibition was absent in seven patients. These results show that the normal human oesophagus responds to distension with a proximal enhancement of propulsive motor activity, mediated through a cholinergic pathway. This may be defective in some patients with disordered oesophageal transit. Investigation of the motor responses to intraluminal distension may thus be a useful adjunct to standard manometry for studying patients with suspected oesophageal clearance dysfunction and might allow identification of disordered enteric nervous control.     

Effects of Neural Blocking Agents on Motor Activity and Secretion in the Proximal and Distal Rat Colon: Evidence of Marked Segmental Differences in Nicotinic Receptor Activity

Background: Neuromodulation may be a new therapeutic approach in inflammatory bowel disease, but very little is known about neural control of colonic secretion in vivo. We therefore determined the effects of neural blockade on colonic motor activity and mucosal secretion in anaesthetized rats. Methods: A proximal and a distal colonic segment were isolated in four groups of chloralose-anaesthetized rats (n = 8 in each group), and we measured luminal pressure and transmural potential difference (PD) as a marker of electrogenic chloride secretion. Recordings were made from proximal and distal segments simultaneously, which made it possible to directly compare response patterns. Results: Under control conditions luminal pressure waves were associated with phasic, lumen-negative increases in PD which had a significantly greater magnitude and longer duration in the distal colon. Atropine blocked both pressure waves and PD waves in the proximal colon, but some PD waves, although of lower magnitude, remained in the distal colon. Hexamethonium abolished pressure waves in both segments and induced a marked reduction in PD in the distal but not in the proximal colon. Lidocaine also reduced PD, more so in the distal colon, and dissociated the pressure-PD linkage. Conclusion: In the distal but not in the proximal colon, there is a strong nicotinic, neurogenic `tone' that maintains a high basal secretory activity. The results encourage the search for neuromodulatory agents in the treatment of colonic secretory disease.     

Effects of neural blocking agents on motor activity and secretion in the proximal and distal rat colon: evidence of marked segmental differences in nicotinic receptor activity

BACKGROUND: Neuromodulation may be a new therapeutic approach in inflammatory bowel disease, but very little is known about neural control of colonic secretion in vivo. We therefore determined the effects of neural blockade on colonic motor activity and mucosal secretion in anaesthetized rats. METHODS: A proximal and a distal colonic segment were isolated in four groups of chloralose-anaesthetized rats (n = 8 in each group), and we measured luminal pressure and transmural potential difference (PD) as a marker of electrogenic chloride secretion. Recordings were made from proximal and distal segments simultaneously, which made it possible to directly compare response patterns. RESULTS: Under control conditions luminal pressure waves were associated with phasic, lumen-negative increases in PD which had a significantly greater magnitude and longer duration in the distal colon. Atropine blocked both pressure waves and PD waves in the proximal colon, but some PD waves, although of lower magnitude, remained in the distal colon. Hexamethonium abolished pressure waves in both segments and induced a marked reduction in PD in the distal but not in the proximal colon. Lidocaine also reduced PD, more so in the distal colon, and dissociated the pressure-PD linkage. CONCLUSION: In the distal but not in the proximal colon, there is a strong nicotinic, neurogenic 'tone' that maintains a high basal secretory activity. The results encourage the search for neuromodulatory agents in the treatment of colonic secretory disease.     

Distribution and spread of colonic lesions in shigellosis: a colonoscopic study

In a study of the distribution and severity of colonic lesions in patients with shigellosis, colonoscopy was performed for 33 men with this disease. All 33 patients had inflammatory lesions in the rectosigmoid area; in 18 (55%) the lesions extended to the splenic flexure, in 14 (42%) the disease extended to the distal transverse colon, in nine (27%) the area of involvement included the proximal transverse colon, and in five (15%) pancolitis was evident. In most patients lesions were continuous and diffuse, with the intensity of inflammation decreasing in a proximal direction. Biopsied samples from proximal lesions usually showed less severe inflammation than did those from more distal lesions. Aphthoid erosions, which have not previously been described in shigellosis, were observed in five patients. Proximal colitis was associated with diarrhea of four or more days' duration (P less than .01, Fisher's exact test). These findings indicate that the rectosigmoid is the most frequently and most severely affected area of the colon in shigellosis and suggest that during the course of shigella infection, colonic lesions extend in a proximal direction.     

Potential Role of 5HT1C and/or 5HT2 Receptors in the Mianserin-Induced Prevention of Anxiogenic Behaviors Occurring During Ethanol Withdrawal

A single dose of mianserin (a 5HT_1C/5HT₂ antagonist), administered 1 hr, 48 hr, or 7 days before testing, was evaluated for its efficacy in alleviating or preventing the occurrence of anxiogenic behaviors observed during ethanol withdrawal. Other behavioral experiments using selected drug interactions were conducted to examine whether the effect of mianserin was related to a long-term modification of 5-hydroxy-tryptamine (5HT) receptor function. Rats were fed a liquid diet containing 4.5% ethanol for 4 days. They were tested on the elevated plus-maze (EPM) 12 hr (acute withdrawal) and 5 days (protracted withdrawal) after the last ethanol dose. Ethanol withdrawal induced a pattern of “anxiogenic” behavior that consisted of reduced activity (total entries) and a reduced proportion of open arm activity. Mianserin, injected as a single dose given either 1 hr (0.16-5 mg/kg, ip) before testing or given (20 mg/kg, ip) on the morning of the 3rd day of ethanol administration, i.e., 48 hr and 7 days before testing, dose-dependently prevented or reversed the ethanol withdrawal induced reduction in open-arm activity. In contrast, the 5HT₁C/5HT₂ receptor agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane HCI (DOI) did not affect behaviors in the EPM in ethanolnaive rats, nor in those undergoing ethanol withdrawal. However, although there was a marked tolerance to DOI-induced body shakes (a measure of 5HT₂ function) during withdrawal, DOI reversed the action of mianserin in the EPM. The 5HT₁ receptor agonist, 5HT₂ receptor antagonist 1-naphthyl-piperazine (1-NP) reduced open-arm activity in ethanol-naive rats and this action was enhanced during withdrawal. 1-NP reversed the effect of mianserin pretreatment and during ethanol withdrawal the dose-response curve of 1-NP was shifted to the left. The behavioral data indicated a reduced efficacy of 5HT₂ receptors during ethanol withdrawal while anxiogenic behaviors are present, whereas stimulation of 5HT_1C receptors appears anxiogenic. These data support the hypothesis that mianserin may alleviate withdrawal anxiety by direct blockade or down-regulation of 5HT_1C receptors.     

Myoelectric and motor activity of the terminal ileum after pelvic pouch for ulcerative colitis

The electrical and motor activity of the terminal ileum after proctocolectomy and ileoanal reservoir was evaluated in seven patients who had undergone surgery for ulcerative colitis. Recordings were carried out with an intraluminal probe under fasting conditions, during stepwise distention of the pouch, in the postprandial state and after administration of Prostigmine^® and bisacodyl. Ileal sensitivity was also studied. Phase III of the interdigestive myoelectric motor complex, when detectable (four patients), was characterized by regular spike bursts superimposed on slow waves at a frequency of 9 cycles per minute. Two different types of motor patterns were observed: short phasic waves lasting 2 to 6 seconds and long tonic waves lasting up to 2 minutes. In most cases, the amplitude and frequency of the pressure events were higher in the efferent limb than in the reservoir. Electrical activity of the surrounding rectal muscle and striated sphincters was also recorded. When distended to the maximum tolerable volume, the reservoir showed spike bursts propagated aborally at a frequency of 15 per minute, leading to large propulsive waves. An overall increase of spike activity was observed after a meal, which did not affect the slow waves. Neostigmine caused an irregular increase of electrical and motor activity, more evident in the efferent limb. Bisacodyl, used to test the functional integrity of the myenteric plexus, elicited strong propulsive contractions and urgency. Leakage did not occur frequently either at rest or under stimuli. Onset of sensation was elicited with volumes of 271±149 ml (Mean±SD) in the reservoir and 17±6 ml in the efferent loop of small bowel (P<0.001). In conclusion: 1) most of the electrical and motor properties of the terminal ileum are retained after surgery; 2) due to its large capacity, the reservoir acts as a storage organ; and 3) overall motility is reduced in the pouch when compared with the distal ileum and propulsion in the triple-loop system is opposed by the activity of the anal sphincters.     

Decrease in Gastric Sensitivity to Distension by 5-HT1A Receptor Agonists in Rats

Using an in vivo model for evaluation of gastricsensitivity in awake rats, we aimed to determine whether5-hydroxytryptamine 1A (5-HT_1A) agonistsmodify pain threshold and gastric compliancespecifically through 5-HT_1A receptors. Isobaricgastric distensions were performed with a barostat usingsteps of 5 mm Hg in male rats equipped with a gastricballoon and electrodes implanted in the neck muscles.Gastric distension at 15 or 20 mm Hg induced a typicalposture associated with contractions of the neckmuscles. Rats received drugs 30 min before gastricdistension. The 5-HT receptor agonist8-hydroxy-2-(di-n-propylamino)tetra1A lin (8-OH-DPAT),administered intraperitoneally (0.5 mg/kg) increasedgastric pain threshold and gastric tone. These effectswere reproduced when administered centrally (0.05 mg/kg) and blocked by intracerebroventricularadministration of the 5-HT_1A antagonist WAY100635. Flesinoxan (4 mg/kg, intraperitoneally), another5-HT_1A agonist reproduced the effects of8-OH-DPAT on pain threshold and gastric tone and the alpha-receptorantagonist yohimbine did not modify the action of8-OH-DPAT. Our results indicate that activation of5-HT_1A receptors at the level of the centralnervous system increases gastric tone and decreases gastric sensitivityto distension.     

Colorectal Motility Induction by Sacral Nerve Electrostimulation in a Canine Model

PURPOSE: This study investigated the role of the sacral nerves in the mechanism of defecation using adult mongrel dogs. The possibility of designing a colonic pacemaker as a new therapeutic device to treat defecation disturbances, such as fecal incontinence and severe constipation, is also discussed. METHODS: Colorectal motility during spontaneous defecation was monitored with force strain-gauge transducers implanted in the proximal, distal, and sigmoid colon, rectum, and internal anal sphincter. Under general anesthesia, the sacral nerve was stimulated electrically, and the colorectal motility response was examined. RESULTS: During spontaneous defecation, three characteristic motility patterns were observed: 1) giant migrating contractions of the colon were propagated to the rectum or anus; 2) the rectum relaxed before the giant migrating contractions were propagated; and 3) the internal anal sphincter was relaxed during the propagation of the giant migrating contraction. Sacral nerve stimulation elicited the following three unique responses: 1) contractile movements were propagated from the distal colon to the rectum; 2) a relaxation response was noted in the rectum; and 3) the internal anal sphincter exhibited a relaxation response. The duration and propagation velocity of the contractile responses and the duration of relaxation responses elicited by electrical stimulation of the sacral nerve were similar to those that occurred during spontaneous defecation, but their amplitudes were smaller. CONCLUSION: The coordinated processes of the colon and anorectum during defecation were affected by the sacral nerves. This suggests that it is possible to design a colonic pacemaker to control lower colonic and rectal movements.     

Orphanin FQ, but not dynorphin A, accelerates colonic transit in rats

BACKGROUND & AIMS: The endogenous opiate receptor-like 1 ligand, orphanin FQ (OFQ), which structurally resembles dynorphin A, has been identified. We investigated the mechanism of action of OFQ in the colon and compared it with that of dynorphin A in vivo. METHODS: Colonic contractions were recorded via miniature force transducers implanted on the serosal surface of the rat colon. RESULTS: Intravenous administration of OFQ (0.01-3 nmol/kg) induced contractions in the rat colon in a dose-dependent manner. Colonic contractions induced by OFQ were not affected by extrinsic denervation but abolished by tetrodotoxin. Continuous infusion of OFQ (1 nmol x kg(-1) x min(-1)) and dynorphin A (100 nmol x kg(-1) x min(-1)) induced similar phasic contractions in the proximal colon. However, the contractile activity induced by the 2 peptides differed significantly in the mid and distal colon. Giant contractions induced by OFQ infusion migrated from the mid to distal colon. In contrast, dynorphin A evoked simultaneous contractions throughout the entire colon, which did not migrate aborally. Subcutaneous administration of OFQ (1-3 nmol/kg) accelerated colonic transit, whereas dynorphin A (30-100 nmol/kg) delayed colonic transit. CONCLUSIONS: The results show that OFQ accelerates colonic transit by promoting migrating colonic contractions in rats.