Serotonin excites neurons in the human submucous plexus via 5-HT3 receptors

BACKGROUND & AIMS: Serotonin (5-hydroxytryptamine [5-HT]) is a key signaling molecule in the gut. Recently, the neural 5-HT3 receptor received a lot of attention as a possible target in functional bowel diseases. Yet, the 5-HT3 receptor-mediated changes in properties of human enteric neurons is unknown. METHODS: We used a fast imaging technique in combination with the potentiometric dye 1-(3-sulfonatopropyl)-4-[beta[2-(di-n-octylamino)-6-naphthyl]vinyl]pyridinium betaine to monitor directly the membrane potential changes in neurons of human submucous plexus from surgical specimens of 21 patients. An Ussing chamber technique was used to study 5-HT3 receptor involvement in chloride secretion. RESULTS: Local microejection of 5-HT directly onto ganglion cells resulted in a transient excitation of enteric neurons characterized by increased spike discharge. This response was mimicked by the 5-HT3 receptor agonist, 2-methyl-5-HT, and blocked by the 5-HT3 receptor antagonist, tropisetron. The proportions of 5-HT-responsive nerve cells per ganglion ranged from 25.5% +/- 18.4% in the duodenum to 54.2% +/- 46.9% in the colon. Interestingly, 2-methyl-5-HT did not evoke chloride secretion in the human intestine but it did in the guinea-pig intestine. Specific 5-HT3A and 5-HT3B receptor subunit immunoreactivity as well as 5-HT3A and 5-HT3B receptor-specific messenger RNA were detected in the tissue samples. Based on co-labeling with the pan-neuronal marker HuC/D we conclude that submucous nerve cells potentially express heteromeric 5-HT3A/B receptors. CONCLUSIONS: We show that 5-HT excited human enteric neurons via 5-HT3 receptors, which may comprise both 5-HT3A and 5-HT3B receptor subunits.     

Giant diverticulum of the sigmoid colon.

The giant colonic diverticulum is a very rare clinical entity usually located in the sigmoid colon of elderly patients. A case of an 87-year-old woman recently treated in our hospital is reported hereinafter. The patient was non-surgically treated due to her advanced age and high surgical risk.     

Effect of insulin hypoglycemia on the human sigmoid colon

Summary 1. The effect of insulin hypoglycemia on sigmoid activity was studied in 8 normal subjects by the use of small balloons and open-ended catheters. On separate occasions, colonic activity was studied in 4 of these subjects following intravenous glucagon.2. When compared to the preinsulin level of activity, the response to insulin was biphasic, consisting of a depression phase during the 30- to 60-min. period and an excitatory phase during the 150- to 180-min. period. When compared to control (no injection) and placebo (saline) experiments, only the depression phase was significant.3. No difference was observed in the effect of glucagon-free insulin and commercial insulin on colonic activity.4. A positive correlation was observed between blood sugar levels and colonic activity following intravenous insulin.5. Following intravenous glucagon, the number of waves was increased during the 0- to 30-min. period when comparison was made to the pre-glucagon level and to the same time interval in the placebo and insulin studies.The authors wish to acknowledge the invaluable assistance of Drs. Thomas E. Machella and Frank P. Brooks in carrying out this investigation.     

Elastosis in diverticular disease of the sigmoid colon.

Diverticular disease of the sigmoid colon is an increasingly common clinical problem in the ageing population of western industrialised countries but the mechanism by which the disease develops remains unknown. The muscular abnormality is the most striking and consistent feature and this has been studied by light and electron microscopy in 25 surgical specimens of uncomplicated diverticular disease and in 25 controls. This is the first ultrastructural study of human colonic muscle to be published and shows that the muscle cells in diverticular disease are normal; neither hypertrophy nor hyperplasia is present. There is, however, an increase in the elastin content of the taeniae coli by greater than 200% compared with controls: elastin is laid down between the muscle cells and the normal fascicular pattern of the taeniae coli is distorted. There is no alteration in the elastin content of the circular muscle. As elastin is laid down in a contracted form, this elastosis may be responsible for the shortening or 'contracture' of the taeniae which in turn leads to the characteristic concertina-like corrugation of the circular muscle. Such a structural change could explain the altered behaviour of the colon wall in diverticular disease and its failure to change on treatment with bran.     

Adenocarcinoma in tubular duplication of the sigmoid colon.

A rare case of mucus-secreting adenocarcinoma in a tubular duplication of the sigmoid colon is presented. The pertinent radiographic manifestations were: a calcium containing soft tissue mass located at the blind end of a 20 cm barium filled tubular duplication originating at the sigmoid colon.     

Myoelectrical activity and intraluminal flow in human sigmoid colon

Myoelectric spike bursts were recorded in the sigmoid colon by means of an intraluminal silastic tube equipped with 3 Ag–AgCl ring electrodes fixed 15 cm apart on the tube that was introduced by flexible sigmoidoscopy. In six subjects, the tube was also equipped with three catheters whose tip opened 1 cm aborad from each electrode, for pressure recordings. In six other subjects, the tube was equipped with both electrodes and a catheter opening at the tip of the probe for infusing fluids at a rate of 12 ml/min into the colonic lumen. The fluid was collected with another tube inserted in the rectum and the volume was measured at 1-min intervals. Colonic spiking activity was made of rhythmic stationary bursts (RSB) and of sporadic bursts that were either propagating (SPB) or not propagating (SNPB). All sporadic bursts were associated with intraluminal pressure waves whose amplitude was significantly higher than that associated with rhythmic bursts. In the infusion experiments, the volume of fluid collected did not change significantly whether rhythmic bursts were present or not (3.9±1.7 ml/min and 3.3±1.9 ml/min respectively) (mean±sd). However, the volume was significantly higher when sporadic nonpropagating bursts were present (9.4±4.1 ml/min), and even higher when the sporadic bursts were propagating (21.6±8.8 ml/min). These results indicate that (1) the occurrence of sporadic bursts, particularly when propagating, is associated with intraluminal pressure waves that lead to significant propulsive movements; and (2) rhythmic bursts do not seem to be involved in colonic propulsive activity.This work was supported by the grant DG282 from the Medical Research Council of Canada.     

Amyloidosis localized in the sigmoid colon

A 79-year-old woman was admitted to our hospital presenting with bloody stool. Colonoscopic examination showed many irregularly-shaped discrete ulcerations in the sigmoid colon extending for a length of 6cm, situated 16cm proximal to the anl ring. Histopathology of the biopsy specimen in and around the ulcerations revealed the deposition of amyloid materials in the proper mucosa and the submucosa. Similar ulcerations were not detected by endoscopy in other parts of the gastrointestinal tract, i.e., esophagus, stomach, and duodenum. Multiple biopsy specimens taken from various parts of the gastrointestinal tract other than the sigmoid colon showed no amyloid deposition. Further investigations showed no particular abnormality in any organs and the patient was free of such systemic disease as myeloma or collagen disease. The findings were consistent with those of localized sigmoid amyloidosis. Localized colonic amyloidosis is rare, this being the fifth patient reported in Japan in the past 15 years.     

Psychosensory modulation of colonic sensation in the human transverse and sigmoid colon

Psychosensory stimulation increases the perception of stimuli in different regions of the human colon. The aim of this study was to determine the perception of pain and gas during distention of two colonic regions in healthy volunteers during stress and relaxation. In 22 healthy subjects, phasic distentions of transverse and sigmoid colon were performed using infinitely compliant balloons, and symptoms were measured before and during one of three randomized treatments: sham or active relaxation or mental stress. Anxiety ratings and somatic cold-pain sensitivity were included in a multivariate regression model. Mental stress increased levels of anxiety (P < 0.05) and the sensation of gas (P < 0.01), but not pain (P = NS), during transverse colon distentions and the sensations of gas and pain during sigmoid distentions (P < 0.05). Active relaxation reduced only sensation of gas in the sigmoid colon. Somatic pain sensitivity and pretreatment colonic sensory scores were significantly associated with the sensory scores during treatments. Psychosensory stimulation increases colonic sensation during short-term distention in two regions of the human colon; relaxation alone exerts a smaller influence on sensations arising in the sigmoid colon.     

Volvulus of the sigmoid colon in Jordan

This report discusses 27 patients with sigmoid volvulus treated at Jordan University Hospital (JUH) during a 15-year period. These patients represented 4.7 percent of adult patients treated for intestinal obstruction in the same period. The average age was 54.5 years, and none of the patients was institutionalized. Twenty-five patients presented with acute symptoms, and two had chronic symptoms. Sigmoidoscopic detorsion was achieved in 15 patients. Emergency resection was required in two of these patients: for the development of gangrene a few hours after detorsion in one patient and for recurrence within 24 hours in the other despite the presence of a rectal tube. Early recurrence occurred in two other patients and was managed endoscopically. Emergency surgery was performed in 10 other patients: for a failed endoscopic detorsion in three patients, for ulcerated and bleeding mucosa forecasting gangrene in another, and as a primary treatment in six patients who were either misdiagnosed or suspected to have gangrenous bowel. Elective resection was performed in 13 patients. The mortality rate was 15 percent (4/27) for the whole series and 33.3 percent (1/3) for those with gangrenous bowel.     

Neurochemical features of endomorphin-2-containing neurons in the submucosal plexus of the rat colon

AIM:To investigate the distribution and neurochemical phenotype of endomorphin-2(EM-2)-containing neurons in the submucosal plexus of the rat colon.METHODS:The mid-colons between the right and left flexures were removed from rats,and transferred into Kreb's solution. For whole-mount preparations,the mucosal,outer longitudinal muscle and inner circularmuscle layers of the tissues were separated from the submucosal layer attached to the submucosal plexus. The whole-mount preparations from each rat mid-colon were mounted onto seven gelatin-coated glass slides,and processed for immunofluorescence histochemical double-staining of EM-2 with calcitonin gene-related peptide(CGRP),choline acetyltransferase(Ch AT),nitric oxide synthetase(NOS),neuron-specific enolase(NSE),substance P(SP) and vasoactive intestinal peptide(VIP). After staining,all the fluorescence-labeled sections were observed with a confocal laser scanning microscope. To estimate the extent of the co-localization of EM-2 with CGRP,Ch AT,NOS,NSE,SP and VIP,ganglia,which have a clear boundary and neuronal cell outline,were randomly selected from each specimen for this analysis. RESULTS:In the submucosal plexus of the mid-colon,many EM-2-immunoreactive(IR) and NSE-IR neuronal cell bodies were found in the submucosal plexus of the rat mid-colon. Approximately 6 ± 4.2 EM-2-IR neurons aggregated within each ganglion and a few EM-2-IR neurons were also found outside the ganglia. The EM-2-IR neurons were also immunopositive for Ch AT,SP,VIP or NOS. EM-2-IR nerve fibers coursed near Ch AT-IR neurons,and some of these fibers were even distributed around Ch AT-IR neuronal cell bodies. Some EM-2-IR neuronal cell bodies were surrounded by SP-IR nerve fibers,but many long processes connecting adjacent ganglia were negative for EM-2 immunostaining. Long VIP-IR processes with many branches coursed through the ganglia and surrounded the EM-2-IR neurons. The percentages of the EM-2-IR neurons that were also positive for Ch AT,SP,VIP or NOS were approximately 91% ± 2.6%,36% ± 2.4%,44% ± 2.5% and 44% ± 4.7%,respectively,but EM-2 did not co-localize with CGRP. CONCLUSION:EM-2-IR neurons are present in the submucosal plexus of the rat colon and express distinct neurochemical markers.