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PubMed1998

Strain gauge transducer technique for investigation of the pathophysiology of postoperative colonic ileus in awake rats.

Postoperative inhibition of colonic motility is a major contributor to postoperative ileus, but only limited information is available on its pathophysiology. We developed a model to record perioperative gastrointestinal motility in awake rats and investigated the effect of nitric oxide (NO) synthesis blockade on postoperative colonic ileus in rats. Rats were equipped with an i.v. catheter. Two strain gauge transducers were sutured to the colon, and the effects of NO synthesis blockade on postoperative colonic motility were investigated. NO synthesis blockade slightly increased baseline colonic motility. Abdominal surgery profoundly inhibited colonic motility. Blockade of NO synthesis did not prohibit intraoperative inhibition of colonic motility, but significantly hastened recovery of postoperative colonic ileus compared to vehicle. We established a model to record gastric, small intestinal and colonic motility in awake rats postoperatively. Laparotomy and short manipulation of the cecum produced a prolonged inhibition of colonic motility. Inhibition of NO synthesis improved recovery of postoperative colonic motility, indicating that NO partly mediates postoperative colonic ileus in rats.

Animals↗
PubMed1999

Evaluation of the longitudinal musculature of segments of the distal colon interposed following extended jejunum-ileum resection.

Several morbid conditions may necessitate extensive intestinal resection, leading to short-bowel syndrome. When clinical treatment becomes inefficient, a surgical approach is necessary. Distal colon interposition is one of the viable techniques. The interposition of colon segments between remnants of the small bowel improved lifestyle, increased transit time, and diminished diarrhea. The aim of this study is to observe the longitudinal muscular contractions after distal colon interposition. Sixteen male Wistar rats (EPM-1) were submitted to an 80% small bowel resection associated with a partial colectomy of the distal colon immediately after the bifurcation of the middle colic artery followed by a 3-cm isoperistaltic distal colon interposition. After 70 days, the animals were submitted to euthanasia and segments of the jejunum, ileum, remnant colon, and interposed colon were prepared for pharmacological tests. The isometric contractions were measured by a polygraph. After 30 minutes, the dose/effect curves were obtained for both metacholine and barium chloride stimulation through the extraluminal surface (serosa). After this period, we observed a significant increase in the length, diameter, and thickness of the intestinal wall. Regarding the sensibility (pD(2)), no difference was found (interposed colon = 7.21 +/- 0.2; remnant colon = 7.65 +/- 0.1; remnant jejunum 7.46 +/- 0.1; and remnant ileum 7.57 +/- 0.1), even though the animals were submitted to different procedures. In relation to the maximal effect (E(max)), the longitudinal muscle contraction responses (interposed colon = 11.79 +/- 0.1; remnant jejunum = 15.42 +/- 0.2; and remnant ileum = 11.48 +/- 0.2) were lower than those of the remnant colon (E(max) = 22.42 +/- 0.1). This means that there was a possible adaptation of colonic segments to their new location.

Anastomosis, Surgical↗
PubMed1980

The presence of binding proteins for retinoic acid and dihydrotestosterone in murine and human colon tumors.

Retinoic acid-binding protein (RABP), which is distinctly present in embryonic colon and lung, is below the limits of detection in adult mouse colon and lung. The binding protein is present in malignant murine colon tumors as well as in lungs of animals bearing subcutaneously implanted tumors. Primary cell cultures from 1 g of colon tumor 26 gave rise to about 10(7) tumor cells and yielded 30 mg of extractable protein. The lower limit for detection of RABP, based on the appearance of its specific 2S peak after sucrose density gradient sedimentation, was 0.1 mg of protein, which corresponds to 3.3 x 10(4) tumor cells. After subcutaneous implantation of colon tumor 26 in mice, no RABP peak was evident in the lung extracts up to the fourth day. From the fifth day onwards, RABP appeared in lung extracts, possibly as a consequence of pulmonary metastasis. Fragments of mouse lungs containing the metastatic tumor foci were reimplanted subcutaneously and produced tumors that contained RABP at levels comparable to those in colon tumor 26. The primary subcutaneous tumors and pulmonary metastatic tumors showed the same histologic appearance--an undifferentiated carcinoma. On the 15th day of subcutaneous implantation of colon tumor 26 in mice, RABP was detected in lung and brain but in none of the other tissues where the protein is normally undetectable. After intraperitoneal implantation of colon tumor 26 in mice, no well-defined RABP peaks were detected from their liver extracts. None of the three normal human colon extracts analyzed for RABP or a dihydrotestosterone-binding protein (DHTBP) contained any detectable amounts of either of the binding proteins. However, 70% of the human colon tumors contained RABP and 90% contained DHTBP. Both of these binding proteins were evident in the two human colon tissues adjoining colon tumors.

Adenocarcinoma↗
PubMed2002

Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats.

The modifying effect of dietary administration of the polyphenolic antioxidant flavonoid silymarin, isolated from milk thistle [Silybum marianum (L.) Gaertneri], on AOM-induced colon carcinogenesis was investigated in male F344 rats. In the short-term study, the effects of silymarin on the development of AOM-induced colonic ACF, being putative precursor lesions for colonic adenocarcinoma, were assayed to predict the modifying effects of dietary silymarin on colon tumorigenesis. Also, the activity of detoxifying enzymes (GST and QR) in liver and colonic mucosa was determined in rats gavaged with silymarin. Subsequently, the possible inhibitory effects of dietary feeding of silymarin on AOM-induced colon carcinogenesis were evaluated using a long-term animal experiment. In the short-term study, dietary administration of silymarin (100, 500 and 1,000 ppm in diet), either during or after carcinogen exposure, for 4 weeks caused significant reduction in the frequency of colonic ACF in a dose-dependent manner. Silymarin given by gavage elevated the activity of detoxifying enzymes in both organs. In the long-term experiment, dietary feeding of silymarin (100 and 500 ppm) during the initiation or postinitiation phase of AOM-induced colon carcinogenesis reduced the incidence and multiplicity of colonic adenocarcinoma. The inhibition by feeding with 500 ppm silymarin was significant (p < 0.05 by initiation feeding and p < 0.01 by postinitiation feeding). Also, silymarin administration in the diet lowered the PCNA labeling index and increased the number of apoptotic cells in adenocarcinoma. beta-Glucuronidase activity, PGE(2) level and polyamine content were decreased in colonic mucosa. These results clearly indicate a chemopreventive ability of dietary silymarin against chemically induced colon tumorigenesis and will provide a scientific basis for progression to clinical trials of the chemoprevention of human colon cancer.

Animals↗
PubMed1990

Increased levels of phorbin, c-myc, and ornithine decarboxylase RNAs in human colon cancer.

Our previous work on protein kinase C (PKC) and colon cancer has shown altered levels of PKC activity in human colon tumors, as well as activation of PKC by colon tumor promoters such as bile acids. To understand further the role of PKC in colon carcinogenesis, we analyzed the expression of phorbin, a gene induced by PKC activation, in a series of different stages of human colon tumors. As shown by northern blot analyses of poly (A)+ RNA, higher levels of phorbin RNA were seen in 26 colon tumor samples than in their adjacent normal colonic mucosa. There also appeared to be a correlation between the abundance of phorbin RNA in the tumors and the extent of invasion (tumor-to-normal tissue phorbin RNA ratio = 4.2, 8.0, and 11.9 for Dukes' A, B, and C, respectively). Phorbin RNA was also abundant in a human colon cancer line (HT29). We also examined the expression of other mitogen-responsive genes (c-myc, ODC, and beta-actin) in a set of 19 colon tumor samples. All tumors displayed significant (mean 3.8-fold) increases in the level of c-myc RNA compared with their adjacent normal colonic mucosa. About 47% and 16% of these tumor samples also showed increased levels of ODC (mean 3.1-fold) and beta-actin (mean 1.6-fold) RNA, respectively. The increased levels of c-myc, ODC, and beta-actin RNA did not correlate with the extent of tumor invasion. Taken together, these results demonstrate that human colon tumors usually display increased levels of both phorbin and c-myc RNAs. The marked increases in phorbin RNA suggest that this could serve as a useful biomarker in studies on human colon cancer.

Actins↗
PubMed1996

Establishment of human colonic epithelial cells in long-term culture.

Study of normal colonic function is important in understanding the cellular mechanisms of carcinogenesis and other diseases of the colon. However, colonic pathophysiological studies have been limited due to the lack of long-term cultures of normal human colonic epithelial cells. The purpose of the present study was to develop methods of isolating viable human colonic epithelial cells for the establishment of nontransformed colonic epithelial cell lines. Human colonic epithelial cells were isolated from surgically resected normal human colons. We found that the use of a short enzymatic digestion gave a consistently higher number (>90%) of viable human colonic epithelial cells. These isolated colonocytes were grown on plastic, collagen-coated filters, or feeder layers using different media formulations. Those colonocytes from the initial primary cultures that were most "epithelial" in appearance were cloned and passaged to establish long-term cultures of nontransformed human colonic epithelial cells. The epithelial nature and secretory function of these established cell lines were confirmed by morphological criteria (light microscopy,, phase contrast microscopy, and electron microscopy). We found that the long-term cultures remained immunopositive to anti-cytokeratin antibodies and immunonegative to anti-vimentin antibodies. Using a soft agar assay we found that the colonocytes did not form colonies, suggesting that the long-term culturing did not cause these cells to become transformed. Under serum-free conditions, we found that epidermal growth factor and transforming growth factor-alpha were equally potent in their mitogenic effects for these colonocytes. Some of the subcultured cells could be maintained for at least 8 months and still retain their epithelial characteristics. We believe that this methodology will serve as a valuable tool for the isolation and culturing of human colonic epithelial cells for studies of normal and malignant colonic disease processes.

Agar↗
PubMed1998

Role of non-adrenergic non-cholinergic inhibitory nerves in the colon of patients with ulcerative colitis.

The cause of impaired colonic motility in patients with ulcerative colitis (UC) is unknown. The non-adrenergic non-cholinergic (NANC) inhibitory nervous system is one of the most important factors in the enteric nervous system of human gut. To assess the physiological significance of NANC inhibitory nerves in the colon of patients with UC, we investigated the enteric nerve responses of colonic tissues from patients with this disease. Colonic tissues were obtained from the lesional sigmoid colons of six patients with UC. Normal sigmoid colonic tissues obtained from ten patients with colonic cancer were used as controls. A mechanographic technique was used to evaluate in-vitro muscle responses to the electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. NANC inhibitory nerves were found to act on both normal colon and the lesional colon of patients with UC, but colon with UC was more strongly innervated by NANC inhibitory nerves than was the normal colon. These findings suggest that NANC inhibitory nerves play an important role in the impaired motility observed in the colon of patients with UC.

Adult↗
PubMed2003

Environmental factors affect colon carcinoma and rectal carcinoma in men and women differently.

BACKGROUND AND AIMS: Colon cancer is thought to be more closely associated with environmental factors than rectal cancer, but evidence is currently insufficient. We examined whether there are differences in the degree of environmental effect on colon cancer and rectal cancer in Japan. METHODS: We performed a birth cohort analysis for colon and rectal cancers using Japanese vital statistics from 1950 to 1998 and analyzed time trends by cancer site and gender. RESULTS: The mean annual increase in age-adjusted mortality rate from colon cancer was greater than that from rectal cancer and was greater in men than in women. In men left colon cancer showed the greatest rate of increase whereas cancer of the right colon showed only a slight change. Although left colon cancer rapidly increased until the middle 1980s and thereafter showed no change, right colon cancer showed no change until the middle 1980s and thereafter rapidly increased in men. However, the rates of increase in left colon cancer were greater than those in right colon cancer until the middle 1980s, after which a reversal in trend was seen in women. Birth cohort analysis indicates that for all cohorts the mortality rates at the same age were higher in the recent cohorts than in the previous ones. This trend was more marked for colon cancer than for rectal cancer and was stronger among men than among women. CONCLUSION: Colon cancer is more closely associated than rectal cancer with environmental factors, and this association is more pronounced in men than in women. Consequently cancers at these two sites should not be combined in studies of the role of lifestyle factors in causing these neoplasms. Furthermore, the causes of these diseases may differ in men and women.

Adolescent↗
PubMed2002

Segmental variability of ENaC subunit expression in rat colon during dietary sodium depletion.

In rat distal colon, aldosterone has little effect on Na(+) channel (ENaC) alpha-subunit levels but increases the expression of the beta- and gamma-subunits and stimulates electrogenic Na(+) transport. By contrast, the molecular basis of aldosterone's inability to stimulate electrogenic Na(+) transport in the proximal colon is unclear. We therefore compared the effects of hyperaldosteronism secondary to 10 days dietary Na(+) depletion on ENaC subunit expression in rat proximal and distal colon. Northern analyses revealed appreciable and similar levels of alpha-subunit mRNA throughout the colon in control and Na(+)-depleted animals. By contrast, Na(+) depletion substantially enhanced beta-subunit mRNA expression in the distal colon, but had no effect on the low expression levels of beta-subunit mRNA in the proximal colon. Expression of the gamma-subunit, evaluated by PCR, was also restricted to the distal colon of Na(+)-depleted animals. Western analyses demonstrated similar levels of alpha-subunit protein in the proximal and distal colon of both groups of animals, whereas beta-subunit and gamma-subunit proteins were detected solely or predominantly in the distal colon of the Na(+)-depleted animals. Immunocytochemistry confirmed that significant levels of all three subunit proteins only occurred in the apical membrane of surface cells in the distal colon of Na(+)-depleted animals. Our findings are consistent with previous studies demonstrating that aldosterone stimulates electrogenic Na(+) transport in rat distal colon by increasing the expression of beta- and gamma-subunit mRNA and protein, and thus the amount of functional heteromeric ENaC protein in the apical domain. They also show that aldosterone is incapable of stimulating electrogenic Na(+) transport in rat proximal colon (despite the presence of alpha-subunit mRNA and protein) because of its inability to enhance beta- and gamma-subunit expression in this segment.

Animals↗
PubMed2001

Advanced proximal colon cancer.

BACKGROUND: Two recent studies have documented that sigmoidoscopy as a screening tool for colorectal cancers may miss advanced proximal colonic neoplasms. The purpose of this study was to assess the prevalence of distal synchronous lesions in patients with proximal colon cancer. We sought to determine if screening sigmoidoscopy would have missed these proximal colon cancers. METHODS: Data were collected on all patients (n = 305) diagnosed with colorectal cancer over a 6-year period. Patients were stratified by age, sex, tumor location, presenting complaint, AJCC stage, and TNM classification. The colonoscopy results of patients diagnosed with proximal colon cancer were analyzed to determine the incidence of synchronous distal colon lesions. RESULTS: Proximal colon cancer was diagnosed in 88 patients (29%). Of those studied, 45 (54%) did not have synchronous distal lesions detected by colonoscopy. The patients with proximal colon cancer were elderly (mean age 67), had advanced tumor size [59 patients (67%) T3/T4], and had advanced AJCC stages [37 patients (42%) stage III/IV]. Nearly all patients [84 (95%)] with proximal colon cancer were symptomatic. CONCLUSION: In this study, the majority of patients with proximal colon cancer did not have a synchronous lesion in the distal colon. Current screening methods for colon cancer based on sigmoidoscopy would not have identified these proximal lesions. These findings support the incorporation of screening colonoscopy in protocols designed to identify early colon cancer.

Aged↗
PubMed2006

Inhibitory effects and mechanisms of colonic electric stimulation on gastric and rectal tone in conscious dogs.

PURPOSE: Colonic electric stimulation has been shown to alter motor functions of the colon; however, its effects on other organs of the gut have been investigated rarely. METHODS: This study was performed in 12 dogs implanted with one pair of colonic serosal electrodes and a gastric cannula. Experiments were performed to study: 1) the effect of colonic electric stimulation on proximal gastric tone and compliance; 2) the effect of colonic electric stimulation on rectal tone and compliance; 3) the sympathetic mechanism involved in the effects of colonic electric stimulation on gastric/rectal tone. A computerized barostat was used to assess gastric/rectal tone and compliance. RESULTS: Colonic electric stimulation inhibited both gastric and rectal tone with a higher potency in gastric tone. Colonic electric stimulation reduced gastric but not rectal compliance. The inhibitory effect of colonic electric stimulation on gastric tone but not rectal tone was abolished by an adrenergic blockade, guanethidine. CONCLUSIONS: Colonic electric stimulation inhibits both gastric and rectal tone with a higher potency in inhibiting gastric tone. Colonic electric stimulation reduces gastric but not rectal compliance. The inhibitory effect of colonic electric stimulation on gastric tone seems to be mediated by the sympathetic pathway.

Adrenergic Agents↗
PubMed1985

Comparative effects of opiate agonists on proximal and distal colonic motility in dogs.

The colonic motility index was measured in dogs, by using strain-gauge transducers, before and after administration of opiate agonists. Fentanyl, a mu-compound, ethylketazocine (EKC), a kappa-compound, and [D-Ala2,Leu5]enkephalin (DADLE), a delta-agonist, were administered by intravenous (i.v.) or intrathecal (i.t.) routes. Fentanyl (2-10 nmol X kg-1 i.v.) induced a dose-related period of hyperactivity characterized by an increase in both tone and frequency of contractions in the distal portion of the colon, whereas a period of hypomotility following a short-lived period of increased activity was elicited on the proximal colon. Fentanyl (0.1, 0.2 nmol X kg-1 i.t.) had inhibitory effects on both proximal and distal colon. Small doses of EKC (2-4 nmol X kg-1) administered i.t. or larger doses (20-40 nmol X kg-1 i.v.) inhibited colonic motility for a dose-related duration, the effects of EKC being more marked on the distal colon than on the proximal colon. The administration of DADLE, 1-2 nmol X kg-1 i.t., and 40-20 nmol X kg-1 i.v., inhibited and stimulated the colonic contractions, respectively, in both proximal and distal colon. The results demonstrated that the colonic opiate-mediated responses may vary according to the route of administration, the portion of the colon studied and the opioid agonist used. Opiate agonists when administered centrally show a tendency to modulate colonic activity in a similar way whatever the type of agonist.

Animals↗
PubMed1992

Towards a relatively inexpensive, noninvasive, accurate test for colonic motility disorders.

Currently available clinical tests of colonic transit, such as the radiopaque marker method, are useful to detect delayed transit but may be less sensitive for rapid transit. The aim of this study was to develop a relatively inexpensive, noninvasive, accurate test of colonic transit using selected scintigraphic observations within the first 24 hours after ingestion of a pH-sensitive, methacrylate-coated, delayed-release capsule containing 111In-labeled resin pellets. The authors' previously published colonic transit data on 22 healthy subjects, 9 patients with diarrhea-predominant irritable bowel syndrome, and 7 patients with idiopathic constipation and previously unpublished data on 4 patients with carcinoid diarrhea were analyzed. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected combinations or simple summaries of transit. Among combined transit summaries, the emptying rate of the proximal colon was significantly different between healthy and constipation groups; the geometric center of isotope in the colon at 4 hours was significantly greater in the diarrhea group than in healthy controls; the geometric center at 24 hours was significantly lower in the constipation group than in the other two groups. From the logistic discriminant analysis, simple summaries of transit also had significant discriminant value; these included the isotopic contents in the ascending, transverse, and descending colon at 4 hours and the counts in the ascending and transverse colon and stool at 24 hours. At 90% sensitivity, the specificity of the transverse colon counts at 4 hours was 79%, which is identical to the specificity of the proximal colon emptying rate, both adjusted for age. Thus, quantitation of isotopic counts in colonic regions on scans taken at 4 and 24 hours provides an accurate summary of colonic transit, with acceptable specificity at a high sensitivity in the detection of motility disorders of the colon.

Adult↗
PubMed2004

Effect of coconut cake on the bacterial enzyme activity in 1,2-dimethyl hydrazine induced colon cancer.

BACKGROUND: Colon cancer is one of the most common forms of malignant tumors in humans, and its incidence is increasing. Since the intestinal microflora is directly in contact with the colonic cells, the enzymes of the bacterial microflora may also play a role in colon carcinogenesis. We studied the activity of bacterial enzymes in experimental colon cancer. METHODS: Twenty milligrams per kilogram body weight of 1,2-dimethyl hydrazine (DMH) was administered subcutaneously once a week for first 15 weeks and then discontinued. Coconut cake (25%) was mixed in the diet and given to 30 rats to study the diet effect throughout the experimental period. After 30 weeks, the macroscopic findings in the colon as well as the incidence of tumors in 30 rats was recorded in each group and the activity of beta-glucuronidase and mucinase was estimated in the tissues, colon and fecal contents of 10 rats per group. RESULTS: Average number of tumors in the colon as well as the incidence of cancer was significantly increased in DMH-treated rats which was markedly reduced on supplementing coconut cake. DMH injections significantly elevated both the activities of beta-glucuronidase (distal colon, distal intestine, liver and colon contents) and mucinase (colon and fecal contents) as compared to the control rats. The increase in beta-glucuronidase activity may augment the hydrolysis of glucuronide conjugates, liberating the toxins, while the increase in mucinase activity may enhance the hydrolysis of the protective mucins in the colon. Coconut cake supplementation to DMH-treated rats significantly decreased the incidence and number of tumors as well as the activity of beta-glucuronidase and mucinase. CONCLUSIONS: Coconut cake has a protective effect against DMH induced colon cancer by virtue of its ability to lower the activities of the microbial enzymes beta-glucuronidase and mucinase.

1,2-Dimethylhydrazine↗
PubMed2005

Colonic atresia without mesenteric vascular occlusion. The role of the fibroblast growth factor 10 signaling pathway.

BACKGROUND/PURPOSE: Colonic atresia occurs in 1:20,000 live births, offering a neonatal surgical challenge. Prenatal expression of fibroblast growth factor 10 (Fgf10), acting through fibroblast growth factor receptor 2b (Fgfr2b), is critical to the normal development of the colon. Invalidation of the Fgf10 pathway results in colonic atresia, inherited in an autosomal recessive pattern. Classically, disturbance of the mesenteric vasculature has been thought to cause many forms of intestinal atresia. The purpose of this study was to evaluate the role of vascular occlusion in the pathogenesis of colonic atresia. METHODS: Wild type (Wt), Fgf10(-/-), and Fgfr2b(-/-) mutant mouse embryos were harvested from timed pregnant mothers. Immediately following harvest, filtered India ink was infused via intracardiac microinjection. The gastrointestinal tract was dissected, and photomicrographs of the mesenteric arterial anatomy were taken at key developmental time points. RESULTS: Photomicrographs after India ink microinjections demonstrate normal, patent mesenteric cascades to the atretic colon at the time points corresponding to the failure of colonic development in the Fgf10(-/-) and Fgfr2b(-/-) mutants. The mesenteric arterial anatomy of the colon demonstrates no difference between the Wt and mutant colonic atresia. CONCLUSIONS: The absence of embryonic expression of Fgf10 or its receptor Fgfr2b results in colonic atresia in mice. India ink microinjection is a direct measure of mesenteric arterial patency. Colonic atresia in the Fgf10(-/-) and Fgfr2b(-/-) mutants occurs despite normal mesenteric vascular development. Thus the atresia is not the result of a mesenteric vascular occlusion. The patent colonic mesentery of the Fgf10(-/-) and Fgfr2b(-/-) mutants challenges an accepted pathogenesis of intestinal atresia. Although colonic atresia can occur as a result of vascular occlusion, new evidence exists to suggest that a genetic mechanism may play a role in the pathogenesis of this disease.

Animals↗
PubMed2005

Mechanisms of meconium passage: cholinergic stimulation of electromechanical coordination in the fetal colon.

OBJECTIVE: Fetal gastrointestinal function develops in utero, with evidence of enhanced motility near-term. Although colonic passage of meconium in utero may be associated with fetal maturation or stress, little is known of the mechanisms potentiating motility. We assessed the effect of bethanechol, a cholinergic prokinetic agent, on colonic muscle muscular contractile and electromyogram (EMG) activity in the near-term ovine fetus. METHODS: Near-term (130 days, n = 8) singleton ovine fetuses were chronically prepared with vascular catheters and three sets of miniature strain gauges and bipolar EMGs on the serosal surface of the transverse colon, left colic flexure, and distal colon. Following a 60-minute control period, fetuses received intravenous bethanechol (60 microg/kg, Low-Beth; 120 microg/kg, High-Beth) at 60 and 180 minutes. Colonic activity was recorded digitally and analyzed for short-duration (2<SHORT<15 seconds) and long-duration (15<LONG<120 seconds) strain gauge and EMG contractions. Data were expressed as means +/- SEM and analyzed using one-way analysis of variance (ANOVA) and paired t test. RESULTS: During the control period, there was significantly greater SHORT versus LONG strain gauge contractions in all segments (P <.05). As compared to control values, Low-Beth and High-Beth significantly increased SHORT strain gauge contractions in the transverse colon (160 +/- 13 to 201 +/- 36 and 307 +/- 74 spikes/30 min, respectively, P <.05), although not in left colic flexure or distal colon. Bethanecol did not affect LONG strain gauge contractions. SHORT-EMG and LONG-EMG spike bursts did not change in response to bethanecol (280 +/- 20, 59 +/- 2 spikes/30 min, respectively). CONCLUSION: Cholinergic stimulation of fetal sheep colonic activity at 0.9 gestation occurs in the transverse colon, but not the more distal left colic flexure or distal colon. The increased strain gauge, but not EMG activity, suggests that cholinergic stimulation improves electromechanical coordination in the fetal colon. We speculate that cholinergic-induced delivery of gastrointestinal contents to the distal colon evokes local contractile/expulsive mechanisms resulting in meconium passage.

Animals↗
PubMed2000

Decreased expression of nitric oxide synthase in the colonic myenteric plexus of aged rats.

Nitric oxide (NO) is a major non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter in the gastrointestinal tract. NO released from the myenteric plexus enhances colonic transit and facilitates propulsion of the colonic contents by mediating descending relaxation. Although it has been suggested that colonic transit delays with aging, the mechanism of delayed colonic transit in aging remains unclear. We hypothesized that advanced age is associated with decreased expression of neuronal NO synthase (nNOS) and concomitant reduction in synthesis of NO in the rat colon. We studied nNOS mRNA expression, nNOS-immunohistochemistry, nNOS-immunoblotting and NOS catalytic activity in the mid-colon obtained from young (age 4-8 months) and aged (age 22-28 months) Fisher (F344xBN)F1 rats. Western blot analysis of PGP 9.5, a generic neuronal marker, of the colonic tissues were employed to study whether the total number of neurons of the myenteric plexus is reduced with aging. The number of nNOS-immunoreactive cells and nNOS synthesis in the colonic myenteric plexus were significantly reduced in aged rats. In contrast, expression of PGP 9.5 in colonic tissues was not affected in aged rats. Northern blot analysis demonstrated that the expression of neuronal nNOS mRNA was significantly reduced in the colonic tissues in aged rats. Basal and veratridine-induced release of L-[(3)H]citrulline were significantly decreased in colonic tissues from aged rats, compared to young rats. It is suggested that advanced age is associated with diminished gene expression of nNOS, nNOS synthesis and catalytic activity of NOS. This may explain the mechanism of delayed colonic transit observed in advanced age.

Aging↗
PubMed1988

Role of activation of protein kinase C in the stimulation of colonic epithelial proliferation by unsaturated fatty acids.

Some, but not all, studies have suggested that high-fat diets promote colon carcinogenesis, possibly by stimulating the proliferative activity of colonic epithelium. Both the increase in colonic excretion of bile salts and of fatty acids that occur with an increase in fat ingestion have been implicated as stimuli of epithelial proliferative activity. In this study, we examined the role of activation of protein kinase C in fatty acid-induced stimulation of colonic epithelial proliferation in the rat. Intracolonic instillation of arachidonate, linoleate, or oleate at concentrations that did not induce surface cell injury or loss increased colonic mucosal ornithine decarboxylase activity and stimulated incorporation of [3H]thymidine into mucosal deoxyribonucleic acid. The saturated fatty acid palmitate was without effect. Arachidonate, linoleate, and oleate each induced the translocation of protein kinase C activity from the soluble fraction to the membrane fraction of colonic mucosa, an index of enzyme activation. The translocation of protein kinase C induced by unsaturated fatty acids occurred both in vivo after intracolonic instillation of these agents and in vitro upon incubation of isolated colonic crypt epithelium with fatty acids. The effects of the unsaturated fatty acids on both enzyme translocation and colonic epithelial proliferative activity were suppressed by 1-(5-isoquinolinyl)-2-methylpiperazine, an inhibitor of protein kinase C activity. Unsaturated fatty acids directly stimulated soluble colonic mucosal protein kinase C activity when added to the enzyme assay mixture. This action was blocked by 1-(5-isoquinolinyl)-2-methylpiperazine. However, unsaturated fatty acids also increased the breakdown of polyphosphoinositides when added to isolated colonic epithelium. The increase in polyphosphoinositide breakdown resulted in release of diacylglycerol, an endogenous activator of protein kinase C. Thus, unsaturated fatty acids may activate protein kinase C of colonic epithelium through either a direct intracellular effect or through an action on the cell membrane. The results support a role for protein kinase C in the stimulation of colonic epithelial proliferation by unsaturated fatty acids.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗