The effect of adrenalectomy or pharmacological inhibition of adrenocortical function on macromolecule uptake by the new-born rat intestine

1. Bilateral adrenalectomy in 18-day-old rats resulted in an extension by approximately 4 days of the period during which the villous epithelial cells of the small intestine took up polyvinyl pyrrolidone (PVP) of mean mol. wt. 160,000.2. The eventual termination of PVP uptake (;closure') closely resembled normal closure in control animals: the time course of the decline in uptake and the histological changes indicated that more mature ;PVP-impermeable' cells progressively ascended the villi.3. Injection of Metopirone was ineffective in animals 10 days after birth, but when injected after day 13 caused closure within 3 days.4. Metopirone injection significantly reduced the plasma concentration of corticosterone and caused a marked rise in the plasma concentration of deoxycorticosterone.5. Aminoglutethimide injection also produced precocious closure and had an effect similar to Metopirone on the plasma concentrations of corticosterone and deoxycorticosterone.6. Injection of Metopirone or aminoglutethimide increased the relative adrenal weight compared with control animals. Aminoglutethimide was more effective and caused approximately a 100% increase in adrenal weight.     

The influence of specific chemical factors in the solvent on the absorption of macromolecular substances from the small intestine of the new-born calf

1. The absorption, without change, of [(131)I] and [(125)I]solutes of high molecular weight after duodenal infusion has been measured in anaesthetized calves less than 20 hr old by analysis of lymph collected from the thoracic or intestinal duct.2. Factors present in boiled bovine colostrum whey known to be necessary for the rapid absorption of [(131)I]bovine serum gamma-globulin have now been shown to accelerate the passage of [(131)I]polyvinyl pyrrolidone (PVP) of mean mol. wt. 160,000 (K.60) into the lymph in a comparable manner.3. [(131)I]PVP K.30 (mean mol. wt. 40,000) and [(131)I]human serum albumin could be absorbed to some degree in the absence of solvent factors necessary for the absorption of solutes of higher mol. wt. and a large proportion of the solute thus absorbed passed directly into the portal capillaries.4. Lactate and pyruvate and salts of certain lower volatile fatty acids resemble factors in colostrum whey in their facilitation of the absorption of both gamma-globulin and PVP K.60: these active compounds were not however found in colostrum in significant quantities.5. Potassium isobutyrate was the most effective of the compounds tested and at concentrations of 56.7 m-mole/l. generally accelerated absorption to a greater degree than did colostrum whey itself.6. Absorption of both gamma-globulin and PVP K.60 from colostrum whey was characterized by a profuse flow of lymph containing relatively low concentrations of labelled solute. In contrast, when these solutes were fed in solutions containing simple compounds such as potassium isobutyrate they appeared in very high concentrations in the lymph, the flow of which remained relatively scant.7. When [(125)I]PVP was administered in water, little was absorbed. If, however, such an infusion was followed 3 hr later by a duodenal infusion of colostrum, [(125)I]PVP passed into the lymph almost immediately. This response was too rapid for the colostrum to have reached the absorbing cells in the terminal ileum.8. Intravenous infusions of L+lactate have been found to facilitate the absorption of [(125)I]PVP K.60 introduced into the duodenum in water. This indicates that some of the solvent factors which accelerate absorption may reach the terminal ileum via the blood vascular system after they themselves have been absorbed from the upper small intestine.     

The absorption of polyvinyl pyrrolidone by the new-born pig intestine

1. The intestinal absorption of [(131)I]polyvinyl pyrrolidone of mean mol. wt. 160,000 (K. 60) and 40,000 (K. 30) after oral administration has been measured in unsuckled conscious pigs less than 20 hr old. Absorption was assessed by the measurement of the concentration of [(131)I]PVP in venous blood during the 6 hr after feeding and also by the distribution at the end of the experiment of [(131)I]PVP between homogenates of the alimentary tract and homogenates of the rest of the animal.2. The concentration of [(131)I]PVP in the peripheral blood after feeding was dependent upon the mol. wt. of the polymer, when comparable amounts had been absorbed from the intestine. PVP K. 60 attained higher blood concentrations than PVP K. 30 and the blood concentrations of PVP K. 60 were close to the values to be expected if all the material which had left the intestine had remained in the blood. The lower blood concentrations found when PVP K. 30 was fed were associated with the disappearance of labelled solute from the gut and were thus the consequence of the relatively rapid escape of labelled solute from the plasma after absorption had taken place.3. The ability of the intestine to absorb [(131)I]PVP K. 60 declined progressively after birth but did not terminate abruptly unless the animal was fed colostrum. In unsuckled animals the rate and extent of absorption at 3 hr was much greater than at 20 hr after birth, but some absorption was still present at least 65 hr after birth.4. The transfer of PVP K. 60 to the peripheral blood was dependent upon factors in sow colostrum, since significant absorption did not occur when PVP was fed in water or simple salt solutions.5. The factors which accelerated absorption were present in colostrum from the goat, cow and ewe as well as that from the sow; they remained in the whey, but, in contrast to the factors which accelerate absorption in the calf, were largely inactivated by boiling. Similarly, neither phosphate, lactate, pyruvate, nor lower volatile fatty acid salts, which were effective in the calf, accelerated absorption in the pig.6. The absorption of [(131)I]PVP K. 30 was found to be much less dependent upon the composition of the solvent than the absorption of [(131)I]PVP K. 60, although absorption was most rapid when PVP K. 30 was fed in colostrum.     

The relation between L-methionine uptake and sodium in rat small intestine in vitro

1. Uptakes of L-methionine and mannitol by rat jejunum in vitro were measured over test periods from 5 to 120 sec after 30 min pre-test periods in the presence or absence of Na.2. The initial stage in methionine uptake was dependent on the presence of Na(+) and to a lesser extent on the K(+) concentration. In contrast mannitol uptake was independent of Na and K.3. The initial stage in methionine uptake can be reactivated 30-60% within 5 sec by replacing an Na-deficient intestine into an Na-containing medium.4. Initial methionine uptake was greater with a normal intracellular and low medium Na concentration than with a high medium and low intracellular Na concentration. It is suggested that the intracellular Na concentration is a critical factor, more important than the Na gradient, in determining the rate of amino acid transfer across the luminal membrane.     

The influence of thyroid gland on amino acid accumulation and protein synthesis by rat small intestine in vitro

1. A method is described for measuring the accumulation of amino acids and also the extent to which the absorbed amino acids are incorporated into the tissue protein of rings of rat intestine in vitro.2. With this method rat jejunum was found to accumulate a mixture of amino acids to give a concentration in the tissue water which was 2-3 times that in the medium after 8 min incubation. More than 10% of the absorbed amino acids were found to be incorporated into protein.3. In surgically thyroidectomized animals there was no impairment of the capacity of the intestine to accumulate amino acids nor was there any loss of ability to incorporate these amino acids into protein. Similarly, treatment of the thyroidectomized animals with 3,5,3'-triiodothyronine (T(3)) did not produce any significant change either in the rate of accumulation or in the extent of the incorporation of the amino acids.4. The omission of glucose from the incubation medium was found to cause a large increase in the respiration of mucosal slices in the presence of the amino acid mixture. Thyroidectomy significantly reduced this high respiration rate. Treatment of thyroidectomized animals with T(3) restored the respiration to high value.     

Inhibition of diamine oxidase promotes uptake of putrescine from rat small intestine

In blood from the portal vein of anaesthetized rats the levels of histamine and putrescine were 2–3-fold lower compared to arterial blood. Putrescine concentration was increased severalfold and the difference between portal and arterial blood abolished in animals pretreated with the specific diamine oxidase inhibitor aminoguanidine. Histamine concentration was 40% lower in portal compared to arterial blood in animals treated with the mast cell degranulator compound 48/80. In animals pretreated with aminoguanidine, compound 48/80 enhanced the level of histamine and no difference was observed between arterial and portal blood. The amounts of intravenously injected [¹⁴C]-labeled histamine was about 15% lower in portal compared to arterial blood. The uptake of [¹⁴C]-putrescine from the small intestine was estimated. In urine from animals pretreated with aminoguanidine the concentration of [¹⁴C]-putrescine was more than 40-times higher than in control animals corresponding to a calculated uptake of about 7% in aminoguanidine treated animals. Our results suggest that intestinal diamine oxidase clears the blood from diamines and prevents luminal uptake of putrescine. accepted by W. Lorenz     

Age influence on sucrose hydrolysis and on monosaccharide absorption along the small intestine of rat

The consequences of aging on the hydrolysis and absorption of hexoses was assessed in vitro using everted intestinal segments. Glucose and fructose were given either as a mixture of free monosaccharides or as a disaccharide solution (sucrose). The jejuno-ileum of 3- and 24-month-old rats was everted and divided into four equal segments. For each segment, the mucosal medium contained either sucrose (140 mM) or an equimolar mixture of glucose and fructose (70 mM). Monosaccharide concentrations in the mucosal ans serosal media were measured after 1 h of incubation at 37 degrees C. In the young adult, glucose absorption was enhanced when given as sucrose. In contrast, in the aged rat, free glucose or glucose released from sucrose hydrolysis were similarly absorbed. Independently of age, fructose was better absorbed when provided in a mixture of free monosaccharides. The intestinal segments (and especially the ileum), of the aged animals exhibited higher abilities to hydrolyse sucrose and to absorb monosaccharides indicating a normal or increased intestinal hydrolytic activity and absorptive capacity for dietary sugars.     

The effect of lecithin on intestinal cholesterol uptake by rat intestine in vitro

1. Sacs 20 cm long were obtained from the upper half of the small intestine of bile fistula rats (bile duct cannulated 48 hours previously). The sacs were everted, filled with oxygenated phosphate buffer and incubated 1 hr at 37 degrees C in 25 ml. of a buffered micellar solution of oleic acid (0.6 mM), mono-olein (0.3 mM), sodium taurocholate (4.8 mM) and (3)H-labelled cholesterol (0.15 mM) plus glucose (28 mM).2. After incubation the amount of [(3)H]cholesterol taken up by the mucosal tissue was measured. It averaged 200 n-mole/hr.g tissue wet wt. +/- 6 (S.E.).3. Adding 3 ml. whole rate bile with other factors unchanged caused cholesterol uptake to decrease by 50% in confirmation of previous studies.4. Adding purified lecithin obtained from rat liver tissue, and from egg yolks, similarly decreased cholesterol uptake. A significant response was obtained with 2.5 mg liver lecithin (concentration 0.13 mM) and a near maximum response with 15 mg (concentration 0.80 mM). 10 mg lecithin decreased uptake by an amount equivalent to that obtained with 3 ml. whole bile.5. Lecithin is an active component of whole bile causing reduced intestinal cholesterol uptake from micelles.6. The decreased uptake of cholesterol in the presence of lecithin may have been the result of expansion of the cholesterol-containing micelles with consequent reduction in cholesterol permeability.     

Transfer of alanine isomers by rat small intestine

1. A study was made of the transfer of L-alanine, D-alanine and beta-alanine by sacs of everted small intestine of the rat.2. D-Alanine and beta-alanine are transported against a concentration gradient and in this respect resemble L-alanine.3. Transfer of all three isomers was stimulated in presence of glucose, but stimulation was much greater with D-alanine and beta-alanine.4. Transfer of all three isomers was inhibited by galactose.5. The effect of hexoses on amino acid transfer was relatively independent of the effect on fluid transfer.6. L-Methionine inhibited transfer of the three isomers in descending order, L-alanine, D-alanine and beta-alanine, while the magnitude of sarcosine inhibition was in the reverse order.7. At the concentration used (1 mM), L-alanine was transferred mostly by the methionine carrier, and beta-alanine mostly by the sarcosine carrier. D-Alanine occupied an intermediate position.     

The absorption of a mixture of amino acids by rat small intestine

1. The absorption of a mixture of amino acids by the small intestine has been studied in vitro with mucosal slices from rat jejunum. The mixture contained eighteen amino acids and was used at a concentration of 9.5 mM in the incubation medium. The uptake of fifteen of the amino acids was followed in each sample with the aid of an amino acid analyser.2. The endogenous amino acid content of the slices decreased during preparation and further substantial losses occurred when the slices were preincubated for 30 sec before the addition of the amino acid mixture to the incubation medium.3. When the slices were incubated with the amino acid mixture for 4.5 min all of the amino acid studied were accumulated to give concentration ratios of approximately 2.0.4. The amino acids were taken up rapidly by the tissue so that on average 82% of the amino acids absorbed in 4.5 min had already accumulated after one min of incubation.5. The data for individual amino acids revealed no obvious competition between the various amino acids, and the extent to which the various amino acids were accumulated by the tissue was proportional to their concentrations in the mixture.6. When the Na(+) in the incubation medium was replaced by Li(+), the slices accumulated all of the amino acids studied to concentrations significantly higher than those in the incubation medium. However, the concentration ratios obtained with the Li(+) medium were all lower than those obtained with the Na(+) medium and averaged slightly more than 1.5.7. When the Na(+) in the incubation medium was replaced by K(+) there was little amino acid accumulation, although concentration ratios significantly greater than one were achieved for aspartic acid, glycine, histidine and methionine.     

Effect of fluacizine on the uptake of exogenous noradrenalin by the isolated rat vas deferens

Bulletin of Experimental Biology and Medicine -