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Effect of heat stable and heat labile Escherichia coli enterotoxins, cholera toxin and theophylline on unidirectional sodium and chloride fluxes in the proximal and distal jejunum of weanling swine.

Acute, isolated loops of proximal and distal jejunum of weanling swine were exposed to either heat stable porcine Escherichia coli enterotoxin, heat labile porcine Escherichia coli enterotoxin, cholera toxin or theophylline. Unidirectional sodium fluxes in response to heat stable in the proximal jejunum were dependent on the length of time that the intestinal mucosae was exposed to the enterotoxin. Net water, sodium and chloride and unidirectional sodium and chloride flux measurements in the proximal jejunum in response to each agent uniformly indicated that net secretion of fluid and electrolytes was the result of increased unidirectional sodium secretion or blood-to-lumen flux and decreased unidirectional chloride absorption or lumen-to-blood flux. In addition heat stable cholera toxin and theophylline but not heat labile decreased unidirectional chloride secretion a small but significant amount in the proximal jejunum. Sodium and chloride flux measurements in the distal jejunum demonstrated that all four secretory agents could stimulate net secretion of water, sodium and chloride in that region. The response to these secretory agents as measured by sodium and chloride unidirectional flux rates was not similar to changes observed in the proximal jejunum. In the distal small intestine, whereas heat labile cholera toxin and theophylline induced similar qualitative changes in unidirectional sodium and chloride fluxes, that induced by heat stable differed.

Animals↗

The intestinal phase of gastric secretion. Response to liver extract infusion into the proximal jejunum of healthy human subjects.

A Levine tube was placed under radiological control in the stomach, and a thin polyethylene tube in the proximal jejunum of 6 healthy volunteers. The stomach and proximal part of jejunum were perfused for 2 hours with 1% acetylcholine, 20% meat extract (Bovril), and 15% liver extract (LE) alone and in combination with simultaneous infusion of different doses of exogenous pentagastrin intravenously. A significant increase in serum gastrin concentration was found with antral perfusion of LE only, whereas perfusion of the proximal jejunum did not change the basal level of the serum gastrin concentration. No change from control values was observed in gastric acid, and pepsin output on perfusing proximal jejunum with LE alone, or in combination with pentagastrin. Reflux to the stomach varied between 0-1.4%, as determined by addition of radioactive B12 to the perfusates. The experiments showed that gastrin was released from the antrum of the stomach by perfusion with 15 per cent LE, but not from the jejunum under the present experimental conditions. In the present experiments Bovril and acetylcholine perfusions did not cause significant responses from the antrum or from the proximal jejunum.

Acetylcholine↗

Decrease of lactase activity in the small intestine of jejunum-bypassed rats.

The effect of jejunum-bypass operation on lactase in rat small intestine was examined. Three groups of four or five rats were designated as jejunum-bypassed, sham-operated and normal rats. All animals including normal rats received by pair-feeding 5% glucose/1% NaCl for 5 days following the operation; thereafter they were fed ad libitum the laboratory chow diet. Three weeks after the jejunal bypass operation, the proximal ileum exhibited a hyperplasia as evidenced by a concomitant increase in mucosal contents of both total proteins and DNA. The specific activity of lactase in this segment was significantly lower in the operated rats than sham-operated controls, whereas the specific activity of sucrase in this segment was significantly elevated. The reduction of lactase activity was also evident in the proximal jejunal segment as well as in the distal jejunum which was deprived of luminal nutrition, suggesting that some hormonal factor(s) might be involved in the decrease of lactase activity in jejunum-bypassed animals. Electroimmunoassay revealed that the amount of immunoreactive lactase also declined in the operated rats relative to the sham-operated controls. Our results thus suggest that lactase activity in residual ileum is not only unable to compensate for the loss of digestive-absorptive surface of jejunum, but lactase activity even decreases following jejunum-bypass operation.

Animals↗

Indirect immunofluorescence for anti-jejunum antibody detection in celiac disease: comparison among different antigenic substrates.

BACKGROUND: Although anti-endomysium antibodies (EmA) are the most reliable serological markers of celiac disease (CD), there is a need for low-cost methods for screening programs, as clinically silent disease is increasingly recognized. AIM: To evaluate the suitability of monkey, rat and rabbit jejunum as a substrate for the determination of anti-jejunum antibodies (JAB) in CD. METHODS: JAB of IgA class were detected by indirect immunofluorescence on frozen sections of jejunum from monkeys, white rats and domestic rabbits. Sera from 61 untreated adults with biopsy-proven CD and EmA positivity in 57 out of 61 entered the study as true positives, while sera from 60 controls were considered as true negatives. RESULTS: The sections of monkey jejunum showed the characteristic pattern of elongated villous fluorescence, a ring-like positivity of the cryptal basement membrane, an endomysium-like fluorescence along the smooth muscle layers in the tunica muscularis, while pericryptal fluorescence was not so evident on rat and rabbit jejunum. As compared to EmA positivity, the prevalence of JAB on monkey, rat and rabbit tissues was respectively 57/57, 54/57, 52/57. Two sera among 4 Ema negatives proved positive for JAB. No false positivity resulted from EmA and JAB on monkey jejunum, while a lower specificity was found for JAB on rat and rabbit substrates. CONCLUSIONS: Although monkey, rat and rabbit small intestine appeared to be a suitable alternative substrate for determination of IgA-JAB, because of its lower cost and higher availability, it cannot replace monkey oesophagus, and be recommended for wide use.

Journal Article↗

Comparison of ceftibuten transport across Caco-2 cells and rat jejunum mounted on modified Ussing chambers.

Ceftibuten uptake into Caco-2 cells and intestinal brush border membrane vesicles is mediated by the dipeptide transport system (PEPT1). The apical to basolateral transport characteristics of ceftibuten across Caco-2 cells and rat jejunum mounted on a modified Ussing chamber was examined. Mannitol was used as a paracellular marker along with trans-epithelial electrical resistance (TEER) for monitoring tight junction permeability. Transport across Caco-2 cells and rat jejunum mounted on a modified Ussing chamber was linear across the concentration range 0.25-10 mM. The net flux of mannitol and ceftibuten was higher across rat jejunum compared with Caco-2 cells. At a donor concentration of 0.25 mM, ceftibuten transport across Caco-2 cells was found to be pH dependent. Glycyl proline, a dipeptide, and 2,4- dinitrophenol, an energy poison, caused a reduction in the permeability of 0.25 mM ceftibuten across Caco-2 cells. Benzoic acid and adipic acid also inhibited transcellular transport of ceftibuten. At a donor concentration of 0.25 mM, passive paracellular transport accounts for about 60% and the active carrier mediated mechanism accounts for about 40% of ceftibuten transport across Caco-2 cells. None of the inhibitors however, had a significant effect on ceftibuten transport across rat jejunum mounted on a modified Ussing chamber at a donor concentration of 0.25 mM. In the concentration range 0.25-10 mM, ceftibuten is predominantly transported by paracellular mechanisms across rat jejunum and a mixture of active and passive transport across Caco-2 cells.

Animals↗

Effect of 1,25-dihydroxyvitamin D3 on calcium and magnesium absorption in the healthy human jejunum and ileum.

In calcium deficiency states such as chronic renal failure, 1,25-dihydroxyvitamin D3 increases calcium and magnesium absorption toward normal levels. In the present study, the ability of exogenous 1,25-dihydroxyvitamin D3 to increase calcium and magnesium absorption above normal rates in healthy subjects was investigated. Steady-state perfusion studies were performed in 30 cm segments of jejunum and ileum before and after one week of 1,25-dihydroxyvitamin D3 administration (2 micrograms per day, 10 subjects). Serum 1,25-dihydroxyvitamin D concentration increased from 25.8 +/- 2.5 pg/ml to 56.4 +/- 6.6 (mean +/- SEM, p less than 0.05). In the basal state, calcium absorption was significantly higher in the jejunum than in the ileum. Vitamin D administration resulted in a significant increase in calcium absorption which was quantitatively similar in both the jejunum and ileum. The changes in net movement were due to an increase in lumen-to-plasma flux of calcium; the plasma-to-lumen flux remained unchanged. Jejunal magnesium absorption also was enhanced by 1,25-dihydroxyvitamin D3. These studies demonstrate that in healthy persons, exogenous 1,25-dihydroxyvitamin D3 increases calcium absorption in both the jejunum and the ileum, and increases magnesium absorption in the jejunum.

Adult↗

Effect of chemical ablation of myenteric neurons on neurotransmitter levels in the rat jejunum.

We have quantified neurotransmitter changes in the rat jejunum in which the myenteric neurons were ablated by serosal application of benzalkonium chloride. Within 2 days after benzalkonium chloride treatment, there was a 40% reduction in the activity of choline acetyltransferase, a specific marker for cholinergic neurons, and a 25% reduction in the amount of vasoactive intestinal peptide per centimeter length of jejunum. By 15 days, levels were comparable to those in control segments, and by 45 days after myenteric neuronal ablation, levels in treated tissues were twice those in controls. In contrast, we observed no reduction in the amount of leucine-enkephalin per centimeter length of jejunum at early times after benzalkonium chloride treatment, although by 45 days, levels of this neurotransmitter in treated segments of jejunum were more than twice those in controls. Significant increases in muscle thickness and tissue weight were also observed at 15, 30, and 45 days after myenteric neuronal ablation. Thus we have observed that in response to chemical ablation of myenteric neurons in the rat jejunum, there is a thickening of the smooth muscle layers and a compensatory increase in the production of certain neurotransmitters by the surviving neuronal elements in the gut.

Animals↗

Secretory reflexes in ileum and jejunum: absence of remote effects.

We have tested the hypothesis that luminal secretagogues initiate neural reflexes that alter ion transport in small intestinal segments proximal or distal to the site of the secretory stimulus. Effects of secretagogues that act by different mechanisms were studied in vitro by measuring short circuit current (ISC) of ileum or jejunum mounted in a unique flux chamber while proximal mucosa in neural continuity with the tissue was perfused with secretagogues (Na deoxycholate. Escherichia coli STa, 5-hydroxytryptamine, theophylline) or was stimulated electrically (EFS). No proximal stimulus affected distal ISC. We also studied in vivo adjacent segments of ileum or jejunum in neural continuity but with unconnected lumens. In anesthetized rabbits, we measured transmural electrical potential difference and fluid movement (Phenol red marker). Stimulation of proximal segments of ileum or jejunum with STa, or of ileum with 5-HT or Na deoxycholate did not affect distal transport. Stimulation of distal segments of ileum and jejunum with STa or 5-HT, or of jejunum with Ha deoxycholate did not affect proximal transport. We conclude that the secretion caused by luminal secretagogues in the rabbit small intestine is limited to the area of stimulation.

Animals↗

Different modulation of spontaneous activities by nitrergic inhibitory nerves between ileum and jejunum in W/Wv mutant mice.

We compared the spontaneous electrical and mechanical activities between the jejunum and ileum in the W/Wv mutant mouse, where ICC in the myenteric region (ICC-MY) are deficient. Electrical slow waves (SWs) superimposed with spike potentials, and synchronous circular and longitudinal muscle mechanical activities at a regular rhythm under approximately 1 cm H2O were recorded in the jejunum and ileum of wild-type mice. However, in the jejunum and ileum of W/Wv mice, irregular electrical and mechanical activities without discernable SWs were recorded. N-nitro-L-arginine methyl ester (L-NAME) significantly decreased the mean interval of longitudinal muscle contractions from 4.43+/-3.39 to 2.50+/-1.23 s in the ileum of W/W(V) mice. L-NAME also significantly decreased mean coefficient of variance (decreased irregularity) in the intervals from 2.59+/-0.84 to 0.48+/-0.46 in the ileum. Tetrodotoxin also significantly decreased mean interval and coefficient of variance in the ileum. Neither L-NAME nor tetrodotoxin affected contractile activity in the jejunum. These results suggest that enteric nitrergic nerves in the ileum, but not the jejunum, mediate a steady-state inhibition of myogenic activity in W/Wv mice.

Action Potentials↗

Fluorescein transport properties across artificial lipid membranes, Caco-2 cell monolayers and rat jejunum.

Membrane transport characteristics of a paracellular permeability marker fluorescein were evaluated using artificial membrane, Caco-2 cell monolayers and rat jejunum, all mounted in side-by-side diffusion cells. Modified Ringer buffers with varied pH values were applied as incubation salines on both sides of artificial membrane, cell culture monolayers or rat jejunum. Passive transport according to pH partition theory was determined using all three permeability models. In addition to that, active transport of fluorescein in the M-S (mucosal-to-serosal) direction through rat jejunum was observed. The highest M-S P(app) values regarding the active transport through the rat jejunum were observed in incubation saline with pH 6.5. Fluorescein transport through the rat jejunum was inhibited by DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) and alpha-CHC (alpha-cyano-4-hydroxycinnamic acid). Thus, we assume that two pH-dependent influx transporters could be involved in the fluorescein membrane transport through the intestinal (jejunal) epithelium. One is very likely an MCT (monocarboxylic acid cotransporter) isoform, inhibited by specific MCT inhibitor alpha-CHC, while the involvement of the second one with overlapping substrate/inhibitor specificities (most probably a member of the organic anion-transporting polypeptide family, inhibited at least partially by DIDS) could not be excluded.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

The pancreatic polypeptide family and the migrating motor complex of the rat: differential effects in the duodenum and jejunum.

AIM: To investigate the effects of members of the pancreatic polypeptide family on migrating myoelectric complexes in rats in vivo. METHODS: Rats were supplied with bipolar electrodes at 5 (duodenum), 15 and 25 cm (jejunum) distal to pylorus for electromyography. The natural ligands neuropeptide Y, pancreatic polypeptide, peptide YY1-36 and peptide YY3-36 were infused IV at doses of 0.5-400 pmol kg(-1) min(-1). The mechanisms of action were studied after pre-treatment with N(omega)-nitro-L-arginine (L-NNA) 1 mg kg(-1), guanethidine 3 mg kg(-1) and in bilaterally vagotomized animals. RESULTS: PP inhibited myoelectrical activity dose-dependently in both the duodenum (ED50 5.8 pmol kg(-1) min(-1)) and jejunum (2.6 pmol kg(-1) min(-1)). PYY1-36 and PYY3-36 also had inhibitory effect in the jejunum (4.4 and 130 pmol kg(-1) min(-1), respectively). PYY1-36 had no significant effect in the duodenum, whereas PYY3-36 stimulated myoelectrical activity at the highest doses. NPY was without effect. In the jejunum neither L-NNA, guanethidine or vagotomy had any significant influence on the inhibitory effects of PP, PYY1-36 and PYY3-36. In the duodenum, the effect of PP was inhibited by guanethidine, but not L-NNA or vagotomy. The stimulatory effect of PYY3-36 in the duodenum was blocked by L-NNA and vagotomy, whereas guanethidine was without effect. CONCLUSION: Peptides of the PP family modulate small bowel motility differentially. Whereas their general effect is inhibitory in the jejunum, the mixing duodenal compartment is stimulated by PYY3-36, suggested to reflect receptor distribution distinction in the gut. This implicates distribution of distinct receptors in the gut being activated by either peptide.

Animals↗

A correlation of permeabilities for passively transported compounds in monkey and rabbit jejunum.

Permeability measurements were conducted for a series of compounds using in vitro tissue sections from monkey and rabbit jejunum. Jejunal segments were stripped of serosal musculature and mounted in a diffusion-cell system, using previously described methods and equipment. Permeability determinations of radiolabeled compounds ranging over two orders of magnitude in molecular weight were conducted. For the compounds examined, the permeability of the rabbit jejunum was approximately twice that of the monkey. This was in contrast to the relationship implied by the stripped tissue thickness measurements of 0.92 and 0.83 mm for rabbit and monkey, respectively. An investigation of the size of the paracellular space in the jejunum was undertaken to account for this apparent discrepancy in tissue permeability. Scanning electron micrographs of intestinal sections revealed a similar packing density of cells between species; however, a difference was noted in the shape and number of villi per unit area. Comparative measurements of the paracellular volume in both species using mannitol and methoxyinulin as extracellular space markers further suggests that the paracellular junctions are similar in size but more numerous per unit area of rabbit jejunum than that of the monkey. In contrast to passively transported compounds, the active transport of D-glucose was greater in monkey jejunum compared to rabbit tissue segments. When active transport was inhibited by blockade of the sodium pump with ouabain, the passive component of D-glucose transport for both rabbit and monkey tissue was in agreement with the relationship demonstrated above for compounds which are solely transported by passive processes.

Animals↗

Kinetics of mouse jejunum radiosensitization by 2',2'-difluorodeoxycytidine (gemcitabine) and its relationship with pharmacodynamics of DNA synthesis inhibition and cell cycle redistribution in crypt cells.

Gemcitabine (dFdC), a deoxycitidine nucleoside analogue, inhibits DNA synthesis and repair of radiation-induced chromosome breaks in vitro, radiosensitizes various human and mouse cells in vitro and shows clinical activity in several tumours. Limited data are however available on the effect of dFdC on normal tissue radiotolerance and on factors associated with dFdC's radiosensitization in vivo. The purpose of this study was to determine the effect of dFdC on mouse jejunum radiosensitization and to investigate the kinetics of DNA synthesis inhibition and cell cycle redistribution in the jejunal crypts as surrogates of radiosensitization in vivo. For assessment of jejunum tolerance, the mice were irradiated on the whole body with 60Co gamma rays (3.5-18 Gy single dose) with or without prior administration of dFdC (150 mg kg-1). Jejunum tolerance was evaluated by the number of regenerated crypts per circumference at 86 h after irradiation. For pharmacodynamic studies, dFdC (150 or 600 mg kg-1) was given i.p. and jejunum was harvested at various times (0-48 h), preceded by a pulse BrdUrd labelling. Labelled cells were detected by immunohistochemistry on paraffin-embedded sections. DNA synthesis was inhibited within 3 h after dFdC administration. After an early wave of apoptosis (3-6 h), DNA synthesis recovered by 6 h, and crypt cells became synchronized. At 48 h, the labelling index returned almost to background level. At a level of 40 regenerated crypts, radiosensitization was observed for a 3 h time interval (dose modification factor of 1.3) and was associated with DNA synthesis inhibition, whereas a slight radioprotection was observed for a 48-h time interval (dose modification factor of 0.9) when DNA synthesis has reinitiated. In conclusion, dFdC altered the radioresponse of the mouse jejunum in a schedule-dependent fashion. Our data tend to support the hypothesis that DNA synthesis inhibition and cell cycle redistribution are surrogates for radiosensitization. More data points are however required before a definite conclusion can be drawn.

Animals↗

[Oropharyngeal reconstruction with a free jejunum graft after tumour and stenosis resection: an analysis of 53 cases].

The surgical therapy of oropharyngeal carcinoma by means of a free jejunum graft is an established procedure. The application of a monitor segment for postoperative flow control turned out to be a reasonable modification. In this study, we examine the results over a period of 16 years retrospectively. Between 1988 and 2004, 53 patients underwent oropharyngeal reconstructions by means of 58 free jejunum grafts at the clinic for reconstructive surgery in cooperation with the clinic for otorhinolaryngology. All patients were examined postoperatively with the help of a small jejunum loop in the function of a monitor segment to survey flap vitality. Between the 7th and 11th postoperative day the patients were administered Gastrografin to evaluate oesophagojejunal anastomoses. The survival ratio of the transplants in this series amounted to 90.6 %. All anastomoses were initially passable and leak-proof. After a complete loss of the first graft, five patients were successfully reconstructed with a second jejunum graft. In one patient, the vessel anastomoses had to be revised. In two patients, newly formed stenoses were postoperatively treated with a bougie during hospitalisation. In four patients, fistula formation was detected in the follow-up examination. Substantial advantages of the free jejunum graft compared to other alternative free or local tissue transfers are the excellent functional results, the simple local tumour monitoring and the low complication rate.

Adolescent↗

Nutrient utilization by cells isolated from rat jejunum, cecum and colon.

Cells isolated from the jejunum, cecum and colon of rats were used to study the oxidation of nutrients by quantifying the production of 14CO2 from 5 mmols/L 14C-labeled exogenous substrate. In colonic cells, the decreasing order of oxidation was as follows: butyrate greater than acetate greater than propionate, glucose and glutamine. Acetate and butyrate significantly suppressed oxidation of both glucose and glutamine. In cells taken from the cecum, butyrate was oxidized at a greater rate than all other substrates. Cells taken from the jejunum produced CO2 from exogenous substrates in decreasing order as follows: glutamine greater than glucose much greater than acetate, propionate and butyrate. Butyrate oxidation was significantly reduced in colonic cells by 3-hydroxybutyrate, and it was reduced in cecal cells by glucose. Comparisons among the three gut segments showed no differences in glutamine oxidation. Glucose oxidation was greater in cells taken from the colon than from the cecum or jejunum, which were similar. Butyrate and acetate were oxidized at higher rates in cells taken from the cecum and colon than in cells taken from the jejunum, and propionate was oxidized at a greater rate in cells taken from the colon than from the jejunum. These studies demonstrate that relative rates of substrate oxidation differ along the intestinal tract of rats.

Acetates↗

Feeding medium-chain triglycerides to rats decreases degradation of sucrase-isomaltase complex in the jejunum.

We demonstrated previously that feeding a diet containing medium-chain triglycerides (MCT) to rats causes an increase in the sucrase activity in jejunum relative to diets containing long-chain triglycerides (LCT). To explore the mechanism whereby MCT affect jejunal sucrase activity, 7-wk-old rats were fed a high LCT diet for 7 d, and then they were force-fed either the high LCT diet, a high MCT diet or a high carbohydrate (alpha-methylglucoside) diet for the subsequent 12 h. Feeding the high carbohydrate diet produced significantly greater sucrase and isomaltase activities in both upper and lower jejunum than feeding the LCT diet. Feeding the high MCT diet led to significantly greater sucrase activity in the lower jejunum, but isomaltase activity was not elevated. Rocket immunoelectrophoresis revealed that in the lower jejunum of the rats fed the high MCT diet the proportion of sucrase-isomaltase complex to its degradation product (i.e., isomaltase monomer) was elevated, suggesting that dietary MCT affects sucrase activity by retardation of degradation of sucrase-isomaltase. Because the amounts of total bile acids in the upper jejunum were 50% lower in rats fed the high MCT diet relative to animals fed the high LCT diet, it is likely that MCT feeding decreases secretion of bile into the lumen, which in turn decreases degradation of the sucrase subunit of the sucrase-isomaltase complex.

Animals↗

Absorption of polyethylene glycol oligomers (330-1 122 Da) is greater in the jejunum than in the ileum of rats.

Intestinal permeability to polyethylene glycols (PEG) was measured simultaneously in jejunum and ileum of anesthetized rats. Using a mixture of PEG (400, 600 and 1,000), which contained oligomers in the molecular weight (MW) range from 330 to 1122 Da, the MW permeability dependence of the rat small intestine was examined, employing an in situ recirculation perfusion technique. Individual oligomers of PEG were determined by HPLC with refractive index detection. Based on loss of oligomer from the reservoir, the permeabilities of the jejunum and ileum exhibited similar molecular weight dependencies. The apparent permeabilities were inversely proportional to approximately MW2 in both jejunum and ileum (r = 0.99, P < 0.05). In the range studied, a distinct molecular weight cutoff was not identified at either site. Over the molecular weight range from 330 to 1122 Da (and corrected for the length of each segment) the apparent permeability (Papp) of PEG ranged from 29.54 +/- 0.51 (mean +/- SEM, n = 5) to 1.69 +/- 0.08 microns/min in the jejunum, and from 18.97 +/- 0.47 to 0.74 +/- 0.05 microns/min in the ileum, indicating that the absorption of PEG oligomers is significantly greater in the jejunum than in the ileum (P < 0.05). A near constant ratio of jejunal/ileal permeabilities of 1.6 for the various oligomers (MW range from 330 to 990 Da) suggested that the major difference in the two sites is in the number, rather than the size distribution of the aqueous filled channels, possibly due to a difference in effective surface area for absorption.

Animals↗

Inhibition by morphine of prostaglandin-stimulated fluid secretion in rat jejunum.

1 Anesthetized rats (225 to 300 g) were used to study the inhibitory effect of morphine on fluid secreted by the small intestine. 2 Small intestinal fluid secretion was stimulated by infusion of prostaglandin E1 (PGE1) into the aortic arch, the jejunum being more sensitive than the ileum. Infusion of PGE1 2 microgram/min caused maximal net fluid secretion in the jejunum but inhibited net fluid absorption in the ileum. 3 Morphine caused a dose-related inhibition of maximal PGE1-stimulated fluid secretion in the jejunum. At the higher doses of morphine used (5 to 20 mg/kg) the fluid transporting function of the jejunum was restored almost to normal net absorption. 4 The inhibitory effect of morphine on PGE1-stimulated fluid secretion was antagonized by naloxone. Naloxone caused a parallel shift to the right of the dose-response curve for morphine. 5 Two other narcotic analgesics were assayed relative to morphine and their descending order of potency was oxymorphone greater than morphine greater than pethidine. 6 It is suggested that the antisecretory effect of morphine in the small intestine may contribute to its efficacy as an anti-diarrhoeal drug. Further studies on the rat jejunum may show it to be a useful model for predicting narcotic drug activity and as such, may give some insight into the mechanisms of action of these drugs.

Animals↗