Study of the effect of ileal distension on the motor activity of the jejunum, and of jejunal distension on the motor activity of the ileum

BACKGROUND/AIMS: The effect of ileal distension on the jejunal motor activity and ofjejunal distension on the ileal motility have been poorly addressed in the literature. We investigated the hypothesis that distension of either ileum or jejunum would affect the motile activity of the other. METHODOLOGY: Response of jejunal pressure to ileal balloon distension and of ileal pressure to jejunal distension in increments of 2 mL of normal saline were recorded in 18 dogs. The test was performed after individual local anesthetization of the ileum and jejunum and was repeated using saline instead of lidocaine. RESULTS: Ileal distension with 2, 4, and 6mL of saline produced no jejunal pressure response (p >0.05), while 8- and up to 12-mL distension effected jejunal pressure decrease (p<0.05). Jejunal distension up to 6mL did not change ileal pressure (p>0.05); distension with 8, 10, and 12 mL reduced it (p<0.05). Jejunal or ileal pressure responses were maintained as long as ileal or jejunal distension was continued. Distension of the anesthetized ileum or jejunum did not produce significant pressure changes in either. CONCLUSIONS: Jejunal or ileal pressure decrease and presumably hypotonia upon large-volume ileal or jejunal, respectively, distension postulate reflex relationship which we call 'ileal-jejunal and jejuno-ileal inhibitory reflex'. These reflexes appear to regulate chyme flow in small intestine by creating a balance of chyme delivery between the jejunum and ileum. Reflex derangement in neurogenic and myogenic diseases may result in gastrointestinal disorders, a point that needs to be investigated.     

Study of the effect of jejuno-ileal distension on the motor activity of the stomach with evidence of "entero-gastric inhibitory reflex"

BACKGROUND/AIMS: In chronic constipation due to delayed colonic transit, stasis of the ileal contents with resulting ileal distension may occur. The current study investigated the effect of ileal and jejunal distension on the gastric motility, aiming at elucidating the possible existence of a relationship and its role in the flow through the gut. METHODOLOGY: The response of the gastric pressure to ileal and jejunal balloon distension in increments of 2 mL of saline was recorded in 12 mongrel dogs. The test was repeated after separate local anesthetization of the ileum, jejunum and stomach. RESULTS: 2- and 4-mL ileal balloon distension produced no significant gastric pressure response, while 6- and up to 10-mL distension effected decrease of the antral and corporeal pressures (p < 0.05, p < 0.05, respectively). Jejunal distension produced a gastric pressure decline (p < 0.05) with 4 and up to 10 mL of saline. The gastric pressure decrease did not show significant changes with the various distending volumes. It was maintained as long as ileal or jejunal distension was continued. Distension of the anesthetized ileum or jejunum caused no gastric pressure changes, nor did ileal or jejunal distension produce pressure changes in the anesthetized stomach. CONCLUSIONS: The gastric pressure decline and presumably hypotonia upon ileal or jejunal distension with big volumes postulate a reflex relationship which we call "entero-gastric inhibitory reflex". The small intestine is suggested to slow down gastric emptying through this reflex. A balance is thus created between chyme delivery from the stomach and chyme processing by the small intestine. Reflex derangement in neurogenic and myogenic diseases may result in gastrointestinal disorders, a point that needs to be investigated.     

Electrical activity of the intestine of mice with hereditary megacolon and absence of enteric ganglion cells

Mice with a recessive gene which reduces the number of ganglion cells of the large intestine and produces megacolon similar to Hirschsprung's disease were studied. Electrical activity of the small bowel consisted of electrical slow waves and action potentials and showed no difference between the mice with megacolon and their normal siblings. Electrical slow waves and action potentials occurred in the large intestine of both normal and abnormal mice. The principal difference between normal mice and their abnormal siblings was increased incidence of discharge of action potentials associated with uncoordinated phasic contractions superimposed upon tonic contracture of the circular muscle layer of the distal aganglionic segment in the abnormal mouse. The distended colon of the abnormal mouse and the entire length of the normal bowel showed bursts of action potentials which accompanied peristaltic waves of circular muscle contraction. During propulsive motility in the rectum, activation of the circular muscle was preceded by coordinated contraction of the longitudinal muscle only in the normal bowel. Symptoms of megacolon can be accounted for by the absence of spontaneously active inhibitory neurons from the enteric plexuses of the distal segment of the large bowel.     

Effect of urethral stimulation on vesical contractile activity

BACKGROUND: We investigated the hypothesis that urethral stimulation effects vesical contraction. METHODS: Vesical pressure response to urethral balloon distension with normal saline in increments of 1 mL was recorded in 26 healthy volunteers (17 men, 9 women; mean age, 36.9 +/- 9.7 SD years) before and after individual anesthetization of the urinary bladder and urethra. Urethral distension was effected by a 6F balloon-ended catheter introduced per urethra. Vesical pressure was measured by means of a microtip catheter. RESULTS: Vesical pressure recorded gradual increase on increase of urethral balloon distension. Bladder response was maintained as long as urethral distension was continuous. The response showed no significant difference when we distended different parts of the male or female urethrae. Urethral distension after individual vesical and urethral anesthetization effected no change in the vesical pressure. CONCLUSIONS: Urethral distension produced a vesical pressure increase that presumably denotes vesical contraction. Vesical contraction on urethral stimulation by distension is suggested to be mediated through a "urethrovesical stimulating reflex" that seems to facilitate vesical contraction. Provided further studies to be performed in this respect, the reflex may prove to be of diagnostic significance in micturition disorders.     

Effect of rectal distension on the small intestine with evidence of a recto-enteric reflex

BACKGROUND/AIMS: To study the effect of rectal distension on jejunal and ileal motility aiming at the assessment of the possible role of rectal distension induced by constipation on the transport of the material in the gut. METHODOLOGY: The rectum of 16 healthy volunteers (mean age: 38.6 +/- 11.7 years, 10 men, and 6 women) was distended by a balloon filled with water in increments of 50 mL up to 200 mL and the response of the jejunal and ileal pressures was recorded. The test was repeated distending the anesthetized rectum 20 min and 3 hours after anesthetization. RESULTS: Rectal distension with 50 mL of water effected no jejunal or ileal pressure changes (P > 0.05). One hundred-mililitre (100-mL) rectal distension produced decrease of jejunal and ileal pressures (P < 0.05) which lasted as long as distension was maintained. Rectal distension with 150 and 200 mL caused jejunal and ileal pressure response similar to that of the 100 mL distension (P > 0.05). Distension of the anesthetized rectum effected no significant jejunal or ileal pressure changes. CONCLUSIONS: The results were reproducible in the individual subject. The decline of the intestinal pressure upon rectal distension postulates a reflex relationship between the 2 conditions. This reflex nature is evidenced by reproducibility and by its absence on distension of the anesthetized rectum. We termed this reflex relation: "recto-enteric reflex". It is suggested that under normal physiologic conditions the reflex inhibits the intestinal transit, thus giving the rectum time to evacuate itself. Continuous rectal distension, as occurs in inertia constipation, appears to effect enteric hypotonia, a hypothesis which requires further studies.     

Modulation of esophageal contractions by distensionin Vitro

Stimulation of the intrinsic nerves of the esophageal body leads to a twitch of the circular muscle after the end of the stimulation (the esophageal off-response), and the twitch spreads in the distal direction because of a latency gradient in the onset of the off-response between the proximal and the distal esophagus. We investigated the possibility that local input can modulate the basic off-response through intrinsic mechanisms and make it resemble more closely the sequential ring contractions that move boluses in the esophagus of intact animals (esophageal peristalsis). The esophagus up to the aortic arch and down to the gastroesophageal junction was removed from opossums and suspended in an organ bath containing 2 liters of Krebs solution at 36° C. The mechanical activity of the esophagus was recorded by force transducers on the serosal surface of the esophagus 2, 4, and 6 cm above the LES. The intramural nerves of the proximal esophagus were stimulated by electrical pulses with and without distension of the esophagus by inflation of a luminal balloon. Balloon distension increased the latency of the off-response in the distal esophagus, thereby reducing the velocity at which the circular muscle contraction spread through the esophagus. In addition, balloon distension increased the amplitude and the duration of the esophageal circular muscle contraction (both off- and on-responses), and decreased the amplitude of the longitudinal muscle contraction (duration response) and LES response (relaxation response). Similar changes in the esophageal contraction responses were produced by radial stretch of an open preparation of the esophagus from which the mucosa had been removed. The present results demonstrate that intramural mechanisms can modulate the contraction pattern of the isolated esophageal smooth muscle. The observed changes make it likely that radial stretch is an important factor in turning the intrinsic off-response of the esophageal smooth muscle into the sequential ring contraction observed with esophageal bolus transport in the intact animal.This work was supported by a VA Merit Review Grant and by NIH grants AM34986 and AMI1242.     

Study of the motile activity of the small intestine in constipated subjects

BACKGROUND/AIMS: A recent study has demonstrated that rectal balloon distension effected inhibition of jejunal and ileal motility (Shafik, Hepatogastroenterology, 2000). It was hypothesized that rectal distension occurring in rectal inertia constipation might cause enteric hypotonia. This hypothesis was investigated. METHODOLOGY: Twenty-three patients with rectal inertia constipation (18 women, 5 men mean age 38.8 +/- 10.6 SD years) and 10 healthy volunteers (7 women, 3 men, mean age 37.2 +/- 9.8 SD years) were studied. The rectal, jejunal and ileal pressures were measured by means of saline-perfused tubes. The pressure response of rectum, jejunum and ileum to rectal balloon distension in increments of 50 mL of saline was recorded. RESULTS: The mean basal rectal, jejunal and ileal pressures measured in the patients with rectal inertia were significantly (P < 0.05) lower than those of the volunteers. Fifty-milliliter rectal balloon distension caused no rectal, jejunal or ileal pressure response in either the volunteers or patients. One hundred-milliliter distension effected in volunteers a rectal pressure elevation (P < 0.001) and a decline of jejunal (P < 0.05) and ileal (P < 0.05) pressures which were maintained as long as rectal distension was continued. In patients, no significant (P > 0.05) pressure changes were registered from the rectum, jejunum or ileum. Rectal distension with 150 and 200 mL caused balloon expulsion in the volunteers and in patients no significant rectal, jejunal or ileal pressure changes (P > 0.05). CONCLUSIONS: Rectal inertia was associated with reduced jejunal and ileal pressures, presumably indicating the presence of enteric hypotonia. The inertia-hypotonia relationship is proposed to be mediated through the recto-enteric reflex and transmitted by the enteric nervous plexus. The enteric hypotonia is suggested to prolong the intestinal transit, act as a contributing factor in the genesis of constipation and may explain some of its clinical manifestations.     

Temporal relationship between electrical and mechanical activity of longitudinal and circular muscle during intestinal peristalsis

Mechanical activity was recorded in longitudinal and circular directions from isolated segments of intestine from guinea pigs, cats and rabbits. Records were obtained by a modified Trendelenburg method and compared to recordings from more localized areas of gut wall. The latter method revealed that longitudinal and circular contractions recorded from corresponding points of both muscle layers occur simultaneously, rather than sequentially, during peristalsis; hence, the muscle layers are not reciprocally innervated. Furthermore, peristaltic contractions were recorded from segments of intestine from which the mucosa and submucosa had been removed—ie, in the absence of Meissner's plexus. Evidence is also presented, based on simultaneous electrical and mechanical recordings, that peristaltic contractions are controlled primarily by myogenic slow-wave activity. Intestinal peristalsis is concluded to be primarily a myogenic phenomenon which does not differ qualitatively from what has been classically described as segmentation.Supported, in part, by Public Health Services Research Grant AM-06958 from the National Institute of Arthritis and Metabolic Diseases.     

Duodeno-jejunal junction dyssynergia： Description of a novel syndrome

AIM： To investigate the hypothesis that duodeno-jejunal dyssynergia existed at the duodeno-jejunal junction.
METHODS： Of 112 patients who complained of epigastric distension and discomfort after meals, we encountered nine patients in whom the duodeno-jejunal junction did not open on duodenal contraction. Seven healthy volunteers were included in the study. A condom which was inserted into the ist duodenum was filled up to 10 mL with saline in increments of 2 mL and pressure response to duodenal distension was recorded from the duodenum, duodeno-jejunal junction and the jejunum.
RESULTS： In healthy volunteers, duodenal distension with 2 and 4 mL did not produce pressure changes, while 6 and up to 10 mL distension effected significant duodenal pressure increase, duodeno-jejunal junction pressure decrease but no jejunal pressure change. In patients, resting pressure and duodeno-jejunal junction and jejunal pressure response to 2 and 4 mL duodenal distension were similar to those of healthy volunteers. Six and up to 10 mL 1^st duodenal distension produced significant duodenal and duodeno-jejunal junction pressure increase and no jejunal pressure change.
CONCLUSION： Duodeno-jejunal junction failed to open on duodenal contraction, a condition we call ＇duodenojejunal junction dyssynergia syndrome＇ which probably leads to stagnation of chyme in the duodenum and explains patients＇ manifestations.     

Study of the role of the transverse perineal muscles during rectal filling

Background The function of perineal muscles at defecation is poorly addressed in the literature. We investigated the hypothesis that rectal distension effects reflex contraction of four perineal muscles.Patient/methods After rectal balloon distension with carbon dioxide in increments of 20 ml, the responses of electromyographic (EMG) activity of superficial (STPM) and deep (DTPM) transverse perineal muscles as well as the rectal pressure were recorded in 22 healthy volunteers (14 men, age 37.2±6.3 years). Responses were registered again after individual anesthetization of rectum and transverse perineal muscles. Tests were repeated using saline instead of lidocaine.Results/findings Rectal balloon distension in big volumes effected increase of the transverse perineal muscles’ EMG activity and rectal pressure. The more the rectum was distended, the more the rectal pressure and EMG activity of the transverse perineal muscles were increased. The latency showed a gradual decrease upon incremental rectal distension increase. Transverse perineal muscles did not respond to rectal distension after the rectum and perineal muscles had been individually anesthetized, but it responded to saline administration. Response of the muscles was similar in both sides.Interpretation/conclusion Increase of rectal pressure increases EMG activity of transverse perineal muscles. This action seems mediated through a reflex which we call ‘recto-perineal reflex’. Contraction of transverse perineal muscles at defecation presumably supports the perineal floor. It also protects transverse perineal muscles against straining-produced high pressure that is transmitted through the recto-vaginal/-vesical cul de sac to the perineum which may sag down and share in genesis of perineocele, enterocele, or sigmoidocele.     

Neuropeptide Y inhibits excitatory enteric neurons supplying the circular muscle of the guinea pig small intestine

The effect of neuropeptide Y on the motor activity of the circular and longitudinal muscle of the guinea pig small intestine was investigated. Neuropeptide Y (0.3-30 nM) inhibited, in a concentration-dependent manner, the ascending enteric reflex contraction of the circular muscle; both the cholinergic and noncholinergic component of the ascending enteric reflex were suppressed. Neuropeptide Y also blocked nerve-mediated phasic contractions of the circular muscle, induced by dimethylphenylpiperazinium or ceruletide, and abolished the peristaltic movements of the small intestine. Nerve-mediated cholinergic and noncholinergic contractions of the longitudinal muscle, induced by electrical field stimulation, were only slightly depressed by neuropeptide Y. Further analysis showed that neuropeptide Y did not act directly on intestinal muscle but interrupted excitatory pathways of the enteric nervous system. The effect of neuropeptide Y did not involve activation of alpha-adrenoceptors, opioid receptors, or P1 purinoceptors or the release of endogenous factors stimulating these receptors. These findings suggest a possible physiologic role of neuropeptide Y as a nonnoradrenergic inhibitory transmitter involved in the enteric nervous control of intestinal circular muscle activity.     

Study of the motile activity of the colon in rectal inertia constipation

BACKGROUND: We have recently demonstrated that rectal distension effected left colonic contraction, which probably acts to feed the rectum with fecal matter each time the rectum distends and evacuates its contents. This effect was postulated to occur through the recto-colic reflex. As the colonic status in rectal inertia constipation was scarcely addressed in the literature, we investigated this point. METHODS: The response of the colonic pressure to rectal balloon distension in increments of 10 mL of water was studied in 38 patients with rectal inertia constipation (IC) (age 42.6 +/- 14.3 years, 29 women) and 12 healthy volunteers (40.9 +/- 12.2 years, nine women). The rectal and colonic pressures were measured by saline-perfused tubes connected to a pneumohydraulic infusion system. The rectum was distended by a condom applied to the end of a 10-F catheter. RESULTS: The rectal and left colonic resting pressures were significantly lower in the patients than in the controls (P < 0.5, P < 0.05, respectively). In the healthy volunteers, rectal distension up to first rectal sensation produced no significant rectal or colonic pressure changes (P > 0.05, P > 0.05). At urge, rectal and left colonic pressures increased significantly (P < 0.001, P < 0.001, respectively), but there were no changes in the right colonic pressure (P > 0.05). The colonic response lasted as long as the rectum was distended. In IC, patients did not perceive the first rectal or urge sensation up to a rectal balloon filling of 300 mL; there was no rectal or colonic pressure response (P > 0.05, P > 0.05). CONCLUSION: In normal subjects, left colonic contraction on rectal distension probably acts to feed the rectum with fecal material. In IC, the low left colonic resting pressure assumedly points to left colonic hypotonia which appears to aggravate the constipation produced by the inertic rectum. Furthermore, non-response of the left colon to rectal distension probably impedes rectal feeding with fecal matter and enhances constipation.     

Study of the duodenal contractile activity during antral contractions

AIM: To investigate the hypothesis that duodenal bulb (DB) inhibition on pyloric antrum (PA) contraction is reflex. METHODS: Balloon (condom)-tipped tube was introduced into 1st duodenum (DD) and a manometric tube into each of PA and DD. Duodenal and antral pressure response to duodenal and then PA balloon distension with saline was recorded. These tests were repeated after separate anesthetization of DD and PA. RESULTS: Two and 4 mL of 1st DD balloon distension produced no pressure changes in DD or PA (10.7 ± 1.2 vs 9.8 ± 1.2, 11.2 ± 1.2 vs 11.3 ± 1.2 on H2O respectively, P > 0.05). Six mL distension effected 1st DD pressure rise (30.6 ± 3.4 cm H2O, P < 0.01) and PA pressure decrease (6.2 ± 1.4 cm H2O, P < 0.05); no response in 2nd, 3rd and 4th DD. There was no difference between 6, 8, and 10 mL distensions. Ten mL PA distension produced no PA or 1st DD pressure changes (P > 0.05). Twenty mL distension increased PA pressure (92.4 ± 10.7 cm H2O, P < 0.01) and decreased 1st DD pressure (1.6 ± 0.3 cm H2O, P < 0.01); 30, 40, and 50 mL distension produced the same effect as the 20 mL distension (P > 0.05). PA or DD distension after separate anesthetization produced no significant pressure changes in PA or DD. CONCLUSION: Large volume DD distension produced DD pressure rise denoting DD contraction and PA pressure decline denoting PA relaxation. PA relaxation upon DD contraction is postulated to be mediated through a reflex which we call duodeno-antral reflex. Meanwhile, PA distension effected DD relaxation which we suggest to be reflex and termed antro-duodenal reflex. It is suggested that these 2 reflexes, could act as investigative tools indiagnosis of gastroduodenal motility disorders.     

Local regulation of postprandial motor responses in ileal pouches

BACKGROUND: Local mechanisms are involved in the postprandial regulation of ileal tone in healthy subjects, but whether these mechanisms affect the postprandial tonic response of ileal pouches has not yet been investigated. AIMS: To study the effect of a meal on pouch tone and phasic motor activity in patients with gut continuity or ileostomy and, in the latter group, the effect of a pouch perfusion with chyme or saline. PATIENTS: Twenty patients with ileal pouches: 10 with gut continuity and 10 with ileostomy. METHODS: Pouch tone and the frequency of phasic volume events were recorded with a barostat under fasting and postprandial conditions and after perfusion of the isolated pouch with chyme or saline. RESULTS: The meal increased pouch tone and the frequency of phasic volume events in the patients with gut continuity, but not in those with ileostomy. Pouch perfusion with chyme induced a greater increase in pouch tone than saline. CONCLUSIONS: The meal stimulated pouch tone and phasic motor activity. These effects were at least partially related to local pouch stimulation by intraluminal contents.     

Testing for and the role of anal and rectal sensation.

The rectum is insensitive to stimuli capable of causing pain and other sensations when applied to a somatic cutaneous surface. It is, however, sensitive to distension by an experimental balloon introduced through the anus, though it is not known whether it is the stretching or reflex contraction of the gut wall, or the distortion of the mesentery and adjacent structures which induces the sensation. No specific sensory receptors are seen on careful histological examination of the rectum in humans. However, myelinated and non-myelinated nerve fibres are seen adjacent to the rectal mucosa, but no intraepithelial fibres arise from these. The sensation of rectal distension travels with the parasympathetic system to S2, S3 and S4. The two main methods for quantifying rectal sensation are rectal balloon distension and mucosal electrosensitivity. The balloon is progressively distended until particular sensations are perceived by the patient. The volumes at which these sensations are perceived are recorded. Three sensory thresholds are usually defined: constant sensation of fullness, urge to defecate, and maximum tolerated volume. The modalities of anal sensation can be precisely defined. Touch, pain and temperature sensation exist in normal subjects. There is profuse innervation of the anal canal with a variety of specialized sensory nerve endings: Meissner's corpuscles which record touch sensation, Krause end-bulbs which respond to thermal stimuli, Golgi-Mazzoni bodies and pacinian corpuscles which respond to changes in tension and pressure, and genital corpuscles which respond to friction. In addition, there are large diameter free nerve endings within the epithelium. The nerve pathway for anal canal sensation is via the inferior haemorrhoidal branches of the pudendal nerve to the sacral roots of S2, S3 and S4. Anal sensation may be quantitatively measured in response to electrical stimulation. The technique involves the use of a specialized constant current generator and bipolar electrode probe inserted in the anal canal. The equipment is generally available and the technique has been shown to be an accurate and repeatable quantitative test of anal sensation.     

Intestinal Growth Adaptation and Glucagon-like Peptide 2 in Rats with Ileal–Jejunal Transposition or Small Bowel Resection

Glucagon-like peptide 2 (GLP-2), produced by enteroendocrine L-cells, regulates intestinal growth. This study investigates circulating and intestinal GLP-2 levels in conditions with altered L-cell exposure to nutrients. Rats were allocated to the following experimental groups: ileal–jejunal transposition, resection of the proximal or distal half of the small intestine, and appropriate sham-operated controls. After two weeks, ileal–jejunal transposition led to pronounced growth of the transposed segment and also of the remaining intestinal segments. Plasma GLP-2 levels increased twofold, whereas GLP-2 levels in the intestinal segments were unchanged. In resected rats with reduced intestinal capacity, adaptive small bowel growth was more pronounced following proximal resection than distal small bowel resection. Circulating GLP-2 levels increased threefold in proximally resected animals, and twofold in the distally resected group. Tissue GLP-2 levels were unchanged in resected rats. The data indicate that transposition of a distal part of the small intestine, and thereby exposure of L cells to a more nutrient-rich chyme, leads to intestinal growth. The adaptive intestinal growth is associated with increased plasma levels of GLP-2, and GLP-2 seems to act in an endocrine as well as a paracrine manner.     

Extrinsic nervous control of retrograde giant contraction during vomiting in conscious dogs

Neural mechanisms controlling retrograde giant contraction during vomiting were studied in six conscious dogs with implanted strain gauge force transducers. The small intestine was divided into proximal (P), middle (M), and distal (D) segments. These segments were transplanted on intact mesenteric neurovascular pedicles. In three dogs, M and D segments were interchanged (group A). In three dogs, P and M segments were interchanged (group B). Before transplantation, apomorphine-induced vomiting caused retrograde giant contractions, starting from the M segment and rapidly migrating to the stomach. However, in group A, even after recovery of interdigestive migrating contractions migration, retrograde giant contractions during vomiting always originated in the distally interchanged M segment and jumped to the P segment without migration to the D segment. In group B, the retrograde giant contraction always originated in the proximally interchanged M segment and successively occurred in the distally interchanged P segment. We conclude that origination and migration of retrograde giant contractions are extrinsically controlled. These motor events during vomiting are thought to be a specific motor function that does not exist in the lower small intestine, and retrograde giant contraction during vomiting may originate in the mid-small intestine.     

Effect of intraesophageal location and muscarinic blockade on balloon distension-induced chest pain

Intraesophageal balloon distension has been introduced recently as a provocative test in the assessment of patients with noncardiac chest pain. In order to examine the effect of balloon location and muscarinic blockade on distension-induced pain, 10 asymptomatic male volunteers were studied on two separate days using a low-compliance perfused manometry system that incorporated a silicone rubber balloon. Five-second-duration balloon distensions using balloon volumes of 2.5, 5, 7.5, and 10 ml of air were performed with the balloon located both 16 cm (proximal site) and 6 cm (distal site) above the lower esophageal sphincter (LES) before and after administration of atropine (10 micrograms/kg intravenously) or placebo in a randomized double-blind fashion. A standardized scoring system was used to assess the balloon distension-induced pain. Pain scores varied directly with balloon volume but were consistently higher with the balloon located at the proximal site versus the distal site. This was not associated with any differences in intraballoon pressures between the two sites; however, contraction amplitude orad to the balloon was greater with balloon distension at the proximal site. Atropine significantly decreased pain sensation scores with the balloon located distally but not proximally. This attenuation was not associated with significant changes in intraballoon pressures; however, contractions orad to the balloon were markedly inhibited by atropine with distal but not with proximal distension. These studies indicate that balloon distension-induced pain varies depending on the location of distension. This difference is not explained by differences in esophageal wall tension at the site of distension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional and cellular heterogeneity of cholecystokinin receptors mediating muscle contraction in the gut

The contractile action of cholecystokinin (CCK) on smooth muscle of the gut is either direct (gallbladder and gastric fundus) or both direct and neurally mediated (small intestine). These regional differences were used to characterize pharmacologically CCK receptors on smooth muscle cells and neurons of the gastric fundus, gallbladder, and ileum of the guinea pig. In circular and longitudinal ileal smooth muscle, tetrodotoxin was used to separate direct from neurally mediated contractile effects. Cholecystokinin receptors on smooth muscle cells were found in all locations. The muscle cells displayed a decreasing order of sensitivity to the C-terminal octapeptide of cholecystokinin as expressed in the median doses, and to the selective cholecystokinin antagonist, proglumide, as expressed in the inhibitory dissociation constants. The median doses of the octapeptide of cholecystokinin ranged from 5.5 nM in gallbladder muscle to 185 nM in circular ileal muscle; the corresponding inhibitory dissociation constants of proglumide ranged from 180 to 437 microM [corrected]. Cholecystokinin receptors on cholinergic neurons were confined to circular and longitudinal ileal muscle; the neurons were 80-300 times more sensitive to the octapeptide of cholecystokinin (D50's 0.5 and 2.3 nM) than the corresponding muscle cells, and 19-21 times more sensitive to proglumide (inhibitory dissociation constants, 20 microM [corrected]). The results provide clear evidence of cellular heterogeneity of cholecystokinin receptors (i.e., difference in sensitivity between muscle cells and neurons from the same location) as well as regional heterogeneity (i.e., difference in sensitivity between muscle cells from various locations).     

The localization of the site(s) of neurotensin release in man and dog

The major source of neurotensin in the gut is the ‘N’ cell and this is found in the highest density in the ileum. The ingestion of food, particularly fat, causes the biphasic release of neurotensin-like immunoreactivity (NTLI) into the circulation. The early peak occurs sooner than expected if it is due to the presence of chyme in the ileum, suggesting that the early release of neurotensin is due to a more proximal concentration of N cells or that neurotensin is released from the ileum by a more proximal stimulus. This paper investigates the site(s) of neurotensin release by studying: three groups of patients with various resections of the small intestine and the fashioning of duodenostomies, jejunostomies and ileostomies; and the dog with chronic gastric, duodenal and ileal fistulae, and following ileal resection. The results indicate that the jejunum and ileum are critical in the release of neurotensin following fat stimulation and that the stomach and duodenum have no direct role. The stimulation of the jejunum by fat causes the early rise of plasma NTLI by releasing neurotensin from the ileum. If chyme is prevented from passing to the distal jejunum the magnitude of the early peak is diminished and the second, later, peak is abolished. The second peak of plasma NTLI is due to the direct luminal stimulation of the distal jejunum and ileum by the products of fat digestion. Ileal resection completely abolishes any release of plasma NTLI in response to fat. It was concluded that the source of neurotensin released by the ingestion of food is the ileum. The release of neurotensin from the distal gut is dependent upon a signal from the proximal to the distal gut. The identity of the signal is unknown, but it is either neural or humoral and previous studies suggest a cholinergic-dependent reflex.