Immunofluorescent localization of cyclic AMP in human jejunum and rat liver and jejunum.
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1. The utilization of some metabolic fuels has been measured in vitro in a preparation of rat jejunum to which the substrates were supplied via the perfusate flowing through the vascular bed. 2. In jejunum from 48 hr-fasted rats, the combined rates of utilization of 1 mM-acetoacetate and 2mM-D-3-hydroxybutyrate are similar to that of 7.5 mM-glucose. 3. The utilization of glucose is reduced in jejunum from animals fasted for 48 hr (45--63% reduction) and also from animals after 3--6 days of diabetes induced by streptozotocin (29% reduction). The addition of ketone bodies or of Na-oleate to the vascular perfusate does not reduce the utilization of glucose by the jejunum of either fed or 48 hr fasted rats. 4. Ketone bodies in the vascular perfusate reduce the oxidation of glucose by the jejunum of fed rats. In the jejunum of 48 hr-fasted rats, ketone bodies completely inhibit the oxidation of glucose so that all the glucose utilized by the tissue is converted to lactate. 5. The findings are discussed in relation to other work and it is concluded that substrates for the oxidative metabolism of the jejunum of fasted rats are likely to be ketone bodies, glutamine and fatty acids; at the same time the utilization of glucose is reduced and its oxidation completely abolished.
Net ion and H2O transport by jejunum adjacent to the ligament of Treitz (proximal jejunum) and midjejunum were measured in vivo by continuous perfusion with HCO3-Ringer solution containing a volume marker. Proximal jejunum secreted Na and H2O, whereas midjejunum absorbed Na and H2O. Both segments secreted CO2 and absorbed K and Cl. D-glucose stimulated absorption of Na and H2O and the transmural electrical potential difference (PD) in both segments, but these changes were not accompanied by alterations in Cl, CO2, or K fluxes. However, the increse in Na absorption caused by 3-O-methylglucose was matched by an increase in Cl absorption. This, in addition to increased tissue lactate concentration after addition of D-glucose, suggests that organic anion maintains electroneutrality for Na transport enhanced by D-glucose. Cholera toxin had no effect on ion transport or PD in proximal jejunum, but cholera toxin stimulated secretion and increased the PD in more distal jejunum. Although proximal jejunum shows spontaneous secretory activity, its capacity for secretion is not as great as more distal small intestine.
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.
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.
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.
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.
Recordings of transmural potential difference (PD) across the jejunum of conscious man in situ are characterised by spontaneous fluctuations of up to 10 mV. In 25 of 31 subjects (comprising seven normal controls and 24 patients under investigation for malabsorption, six of whom had coeliac disease) we observed a clear association between these fluctuations and changes in intraluminal pressure recorded at the same site. The most frequent PD changes were associated with type III pressure waves. These consisted predominantly of large waver (3-1 +/- 0-1 mV; mean +/- SEM, n = 317) which reached maximal amplitude approximately 45 seconds after the pressure peak and had a duration of 120 +/- 3 s, but also included less frequent spikes (0-5 +/- 0-1 mV; n = 110) concurrent with the pressure wave with a duration of 5 +/- 1 s. Although by recording at two sites in the jejunum 10 cm apart we were able to demonstrate that type III pressure waves appeared to be propagated aborally at a median rate of 60 cm per minute, the apparent rates of propagation of the corresponding PD waves were much more variable. The largest PD changes (7-8 +/- 0-4 mV; n = 19), lasting several minutes, were found in association with runs of type I waves (basic rhythm) superimposed on a type III wave. Both pressure and PD activities were suppressed by intramuscular propantheline bromide. Intraluminal pilocarpine caused a transient rise in PD not always accompanied by a change in pressure. Distention of the jejunum by rapid injection of a bolus of isotonic sodium chloride produced a delayed rise in the PD which could be prevented by prior administration of propantheline bromide. Experiments using Thirty-Vella loops of proximal jejunum in conscious dogs confirmed the effect of jejunal distension on the PD and also demonstrated that spontaneous retching is preceded by an increase in the PD. Consideration of these results in conjunction with data from other workers suggests the hypothesis that the larger spontaneous fluctuations in transmural PD in the jejunum of conscious man are caused by changes in electrogenic secretion associated with intestinal motility and mediated by cholinergic mechanisms. The possible association of increased secretory activity with motility may have functions of lubrication as well as diluting and mixing the chyme for easier digestion and absorption.
The quantitative passage of urea-N and ammonia N into an isolated jejunum of the merino sheep was studied within one hour before, and 1, 2, 3, 4 and 5 hours after feeding. The total amount of ammonia-N that passes to the isolated jejunum [to both proximal and distal part] within an hour is small [0.28-0.35 mg h-1], without any significant differences in passage prior to and after feeding. However, urea-N secretion is high, especially secretion to the fore part of the jejunum [ 3.35-3.62 mg h-1]. The passage of urea-N to the rear part of the jejunum is about 1/3 lower than passage to the fore part. Urea solution of higher concentration than in peripheral blood was incubated in the isolated jejunum to study an adverse phenomenon: absorption of urea from intestinal lumen to the blood. The levels of urea in peripheralblood and in incubate reached a balance state within one hour after administration. The data obtained testify to the permeability of the wall of the gut for urea in both directions.
1. This paper describes an investigation of the kinetics of influx of the dipeptide glycylsarcosine and the amino acids glycine and L-leucine into rings of everted hamster small intestine in vitro, in proximal and distal small intestine (jejunum and ileum). Results were expressed per unit wet weight of intestine. 2. At all concentrations studied (0.1--100 mmol/l), influx of glycylsarcosine was more rapid in the jejunum than in the ileum. In contrast, at all concentrations studied, influx of glycine and leucine was more rapid in the ileum than the jejunum. 3. Estimates of the simple diffusion component in total influx were made. This component became increasingly large as the substrate concentration was raised. After correction for simple diffusion, transport of all three substrates conformed to Michaelis-Menten kinetics in both jejunum and ileum. Values for simple diffusion, apparent Kt and Vmax, are reported. 4. Possibly physiological implications of the results are discussed, and it is pointed out that under experimental conditions similar to our own, simple diffusion is too large a component in total influx to be ignored.
An experimental study was conducted on the effect of resection of the jejunum and ileum on gastrin release. The intravenous infusion of L. arginine in a dose of 0.5 g per kg body weight for 30 minutes proved to be most practical in evaluating gastrin release in addition to insulin and glucagon release. Serum gastrin levels in response to this dose of arginine were determined before and three weeks, three months and one year after resection of the jejunum and of the ileum. At three weeks, a significant increase in gastrin levels occurred in bothe the fasting state and after stimulation in dogs with either jejunum or ileum resection. At three months, the elevated gastrin response persisted only in those with jejunum resection. By one year, the gastrin levels had fallen in almost all dogs to approximately the preoperative levels.
Epithelial cell kinetics were studied in an ileal segment after transposition to proximal jejunum. The number of cells per villus column in the transposed ileum increased after 4--7 days to reach values normal for jejunum after 14--30 days. This increase was accompanied by a simultaneous increase in the number of cells per crypt column up to 130% of values in jejunum and ileum in situ. The percentage of labelled crypt cells, after labelling with 3H-thymidine, and the relative size of the proliferative cell compartment in the crypt in the transposed ileum did not differ from values in the ileum in situ at any time interval after surgery. The total proliferative activity per crypt, which was determined by scintillation counting of isolated crypts after 3H-thymidine labelling, increased two-fold from 7 days after surgery. Cell migration studies showed that the increase in the number of villus cells was probably not caused by a change in the life span of the epithelial cells. It seems that the increase in the number of villus cells in ileal epithelium after transposition to proximal jejunum is brought about by an enlargement of the crypt, while the relative size of the proliferative cell compartment in the crypt remains unchanged.
1 Pieces of rabbit jejunum were bathed in Krebs solution at 37 degrees C in an isolated organ bath bubbled with O2 and 5% CO2. The bathing fluid was collected regularly and assayed for prostaglandins. 2 The preparations maintained a continuous sub-maximal muscle contraction, referred to as inherent 'tone'. Prostaglandins E2 and F2alpha were continuously generated by the intestine and released into the bathing fluid. The amounts released first declined over 2 h and then steadily increased. The release was also greater after 48 h storage in the refrigerator and after mechanical damage. 3 There was no change in prostaglandin release when the rabbit jejunum was contractd by acetylcholine or physostigmine or relaxed by adrenaline, hyoscine, papaverine, dinitrophenol, or calcium-free Krebs solution. 4 Addition to the bathing fluid of the prostaglandin precursor, arachidonic acid, did not increase the release of prostaglandins although it contracted the tissue. Thus, output of prostaglandins from the tissue was not limited by substrate concentration but more probably by the capacity of the prostaglandin synthetase. 5 Prostaglandin output was decreased by bubbling the bathing fluid with N2 rather than O2; at the same time the preparation relaxed. 6 Aspirin-like drugs such as indomethacin also decreased or abolished prostaglandin formation and this, too, was accompanied by loss of tone of the isolated preparation. 7 Pieces of rabbit jejunum stored in Krebs solution containing indomethacin initially released little or no prostaglandin into the bathing fluid. However, prostaglandin release increased with repeated washing of the preparation. 8 The results suggest that intra-mural prostaglandin production contributes to the inherent tone of the rabbit jejunum, that trauma increases prostaglandin production and that the inhibitory effects of anoxia are linked with the lack of prostaglandin production and activity. The relevance of these findings to intestinal activity in vivo is discussed.
The influence of intravenously administered synthetic salmon calcitonin on water, electrolyte and calcium fluxes in in vivo rabbit jejunum and ileum was examined. Rabbits were divided into four groups: those receiving (1) saline intravenously while a glucose-free isotonic saline solution perfused the jejunum and ileum; (2) calcitonin intravenously while the same intestinal perfusate was used as in group 1; (3) intravenous saline while 10 mM glucose-isotonic saline solution perfused jejunum and ileum; and (4) intravenous calcitonin while the intestinal perfusate was of the same composition as in group 3. Calcitonin provoked a significant increase in jejunal and ileal water, sodium, and bicarbonate secretion in both the glucose-free and glucose-containing perfusate groups. No influence on calcium movement was noted. These results, similar to findings of Gray et al. (J Clin Invest 52:3084-3088, 1975) in human jejunum, suggest that calcitonin may play a role in the pathogenesis of the watery diarrhea noted in about one-third of patients with medullary carcinoma of the thyroid. In addition, these studies demonstrate the usefulness of the rabbit as an animal model with which to investigate further the effects of calcitonin upon intestinal fluid and electrolyte transport.
We studied the effect of ethanol on glucose and water absorption in vivo. In preliminary experiments, using sodium amytal anesthesia, we found that control animals, whose jejunal segment was perfused without ethanol, required more anesthetic agent than those perfused with ethanol. Thus, to allow for unbiased comparison of the absorption data between the two groups of animals, all absorption studies were carried out on conscious restrained hamsters. We found that ethanol did not influence the permeability of the jejunum to polyethylene glycol (PEG) and meglumine diatrizoate. In addition, ethanol did not influence the time required for the onset of steady-state absorption. Using both the gravimetric and the electrical methods, we were unable to show any measurable osmotic pressure exerted by ethanol (150-1050 mM) on the hamster jejunum. In the absorption studies we found that perfusion of the hamster jejunum with five increasing concentration of ethanol (450-1050 mM) appeared to cause a concentration-dependent depression in steady-state glucose transport. Water transport was depressed only when 4.8% (1050 mM) ethanol was perfused.
In order to study the morphological effects of exposure of the jejunum to low ethanol concentrations, we perfused hamster jejunum with 2.1-4.8% ethanol. Following 45 min exposure, many of the villi developed fluid-filled blisters. To compare these findings to the effect of an inert solute at similar concentrations, we perfused hamster jejuna with mannitol. This caused necrosis of the villus tips but no blister formation. Therefore the blisters were the result of the action of ethanol. The rat jejunum was less resistant to ethanol than that of the hamster. We suggest that the initial insult of the freely permeant ethanol is deep to the epithelium, resulting in accumulation of edema under the epithelium.
Total gastrectomy was performed on purebred beagle dogs and a 30--40 cm jejunal segment was grafted isoperistaltically between oesophagus and duodenum. Histological and histoautoradiographical examinations were carried out and the wall-thickness and the cell-transformation rate in the interponate determined. Despite the isoperistaltic substitute-stomach a muscular wall-hypertrophy of 140% of the interponated jejunum was found. The reason for this hypertrophy is thought to be the result of adhesions and the functional mechanical demands. Histoautoradiographical examinations confirmed that the regeneration time in the substitute-stomach decreased by 70% compared with the normal jejunum. The distinct reduction of cell regeneration in the regeneration in the interponated jejunum could be attributed to the considerable regression of the absorbent performance and to the increase in its mechanical exercises.