An analysis of the mechanism of cessation of uptake of macro-molecular substances by the intestine of the young rat (`closure'')

1. The longitudinal distribution of cells capable of absorbing macro-molecular material has been determined in the small intestine of the young rat by measurements of the uptake of [(125)I]polyvinyl pyrrolidone (PVP).2. PVP uptake was never seen in the duodenum and became restricted to the distal half of the small intestine by the 18th day of life. The subsequent decline to zero in PVP uptake was due to an almost uniform decrease in PVP uptake by the distal half of the small intestine.3. Histological studies indicate that this rapid decline in PVP uptake did not reflect a decrease in uptake by individual cells, but rather their replacement by new cells incapable of taking up PVP.4. Autoradiographic estimates of turnover time in the intestinal epithelium using tritiated thymidine reveal good agreement between the time needed to replace completely the epithelium of the ileum (62 hr) and the duration of the rapid decline in PVP uptake (approximately 3 days).5. It is concluded that on or about the 18th post-natal day there is an abrupt change in the functional characteristics of the apical plasma membrane of cells produced by the crypts of Lieberkühn in the distal half of the small intestine. The stimulus for this change is unknown, but cells produced subsequently cannot take up PVP.     

The use of [125I]polyvinyl pyrrolidone K. 60 in the quantitative assessment of the uptake of macromolecular substances by the intestine of the young rat

1. A method has been developed which allows the quantitative estimation of the uptake of labelled polyvinyl pyrrolidone (PVP) of mean mol. wt. 160,000 (K. 60) by the wall of the small intestine of young rats.2. Four hours after feeding a standard dose of [(125)I]PVP by stomach tube, the small intestine was thoroughly washed out, and the radioactivity of the intestinal wall measured. Under these conditions, the small intestine of animals less than 18 days old took up more than 50% of the radioactivity which had left the stomach. There was no increase in PVP uptake if the duration of absorption exceeded 4 hr. The PVP was taken up by the epithelial cells of the villus, and its intracellular localization has been demonstrated by fluorescence microscopy and can be related to vacuolation in the cells.3. In animals between 18 and 20 days old the uptake of PVP declined progressively, until, in animals more than 20 days old, less than 5% of the radioactivity was taken up by the intestinal wall.4. There is good agreement between the reported age of termination of antibody absorption in young rats and the age at which PVP uptake ceased in the present experiments. It is suggested that the loss of ability of the intestine to take up substances of high mol. wt. may be the factor which limits the duration of the period of antibody absorption in this species.     

The influence of exogenous steroids on macromolecule uptake by the small intestine of the new-born rat

1. Plasma concentrations of cortisol and corticosterone measured by competitive protein binding in rats between 5 and 28 days after birth have been related to the intestinal uptake of [(125)I]polyvinyl pyrrolidone (PVP).2. Plasma cortisol concentration was consistently low throughout the period studied, but there was an increase in plasma corticosterone concentration at the time (18-21 days) when PVP uptake declined to zero (closure).3. Injection of a large dose of cortisone acetate 5 days after birth resulted in precocious closure; PVP uptake declined progressively to zero during the 6 days following the injection. Injection of this steroid at 12 days of age caused closure within 4 days.4. Precocious closure induced by cortisone acetate was closely comparable histologically with natural closure; the decline in PVP uptake was associated with the progressive displacement of vacuolated cells from the villi of the terminal intestine.5. Injection of corticosterone at either 5 or 12 days after birth also reduced PVP uptake. However, the reduction was transient and uptake returned to control levels some days after the injection.6. The temporary reduction in PVP uptake following corticosterone injection was not associated with any change in the histological appearance of the small intestine at the light microscope level.7. The injection of either cortisone acetate or corticosterone was followed by a period of impaired body growth and also a reduction of adrenal weight in animals injected at 12 days but not in animals injected at 5 days.     

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.     

Factors influencing the uptake of [125I]polyvinyl pyrrolidone by the intestine of the young rat

1. The uptake of orally administered [(125)I]polyvinyl pyrrolidone (PVP) of mean mol. wt. 160,000 (K. 60) by the small intestine of young rats was determined 4 hr after feeding by measurement of the radioactivity remaining in the wall after flushing out the intestinal contents.2. PVP uptake was proportional to the administered dose of PVP for doses of 1 mg and below. At higher doses, uptake was no longer in linear proportion, suggesting a degree of saturation of uptake.3. Litters were reared in one of three environmental temperatures: 13, 20 and 30 degrees C, and were tested to determine the age at which PVP uptake ceased (;closure'). The results were evaluated statistically (see Appendix).4. There was no significant difference between the time of closure in animals reared at 20 and 30 degrees C, but, relative to these groups, closure was significantly delayed, by approximately 48 hr, in animals reared at 13 degrees C.5. Once closure had begun, there were no significant differences in the rate of decline in PVP uptake with age between animals reared at different environmental temperatures.6. Separation of the young rats from their mother both before and after the test-feed of PVP caused a considerable reduction in PVP uptake. Provided that the body temperature of the young rats was maintained, the main factor contributing to the reduction in PVP uptake appeared to be the absence of milk, rather than separation from the mother.     

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 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 in-vivo kinetics of lymphoblast localization in the small intestine.

We have studied the in-vivo kinetics of the accumulation of 125I-UdR labelled mesenteric lymphoblasts in the small intestine of mice. The efficiency with which the labelled cells were extracted from the blood and retained by the intestine was quantified by examination of the accumulations observed over the first 4 hr after cell transfer. The kinetic parameters for the uptake and retention of lymphoblasts determined from these early times were found to provide a good approximation to the entire time course of accumulation observed from 1 hr to 22 hr after cell transfer. For normal mice, approximately 1% of lymphoblasts delivered by the blood stream at any given time gained entry to the small intestine and were retained with an average half-time of 6.5 hr. We also studied the accumulation of lymphoblasts in the small intestine of mice undergoing a self-limited enteric infection with the nematode, Trichinella spiralis. There was a greater accumulation of lymphoblasts in the small intestine of these animals. This was the consequence of a prolongation of the half-time for retention of lymphoblasts within the intestine to 15 hr, rather than increased uptake of lymphoblasts from the blood. During a secondary infection with T. spiralis, the half-time for retention of lymphoblasts in the intestine was decreased to 3 hr. These studies show that viewing the accumulation of lymphoblasts as the result of a series of first order kinetic processes provides a suitable model for the migration of lymphoblasts to the small intestine.     

The transamination of glutamate and aspartate during absorption in vitro by small intestine of chicken, guinea-pig and rat

1. Procedures are described for direct measurement of the extent and rate of transamination of glutamate and aspartate over periods of up to 90 min, during absorption in vitro by the small intestine of chicken, guinea-pig, and rat.2. During absorption of dicarboxylic amino acids by rat small intestinal segments circulated through the lumen in vitro, alanine contributed up to 85% of the amino acids appearing in the fluid secreted at the serosal surface. In guinea-pig and chicken intestine, the proportion of alanine in the secreted amino acids did not exceed 60%.3. For the different species studied, a relationship was found between the extent to which the dicarboxylic amino acids were transaminated to alanine and the total amount of GPT found in other studies to be present in the intestinal mucosa. In both rat and guinea-pig small intestine, the proportion of alanine in the total amino acids appearing at the serosal surface was similar in the jejunum and ileum. The rate of appearance of alanine in serosal fluid was greater in the ileum than in the jejunum of the rat.4. Reasons are given for supposing that for all the species studied there is a limit to the capacity of the small intestinal mucosa to subject free dicarboxylic amino acids to transamination. It is concluded, however, that it is unlikely that this capacity will be exceeded under in vivo conditions.     

Distribution of growth-associated protein, B-50 (GAP-43) in the mammalian enteric nervous system

The presence of the growth-associated protein, B-50 (also known as GAP-43) was investigated in the adult mammalian enteric nervous system. The small intestine of rat, ferret and human was examined by immunohistochemistry. Dense B-50-like immunoreactivity was localized in nerves throughout the wall of the rat, ferret and human small intestine, notably in the myenteric and submucous plexuses, where in the ferret ileum it co-localized with vasoactive intestinal polypeptide-immunoreactive fibre groups. Material with the biochemical and immunological characteristics of rat B-50 was extracted from the rat ileum. In-situ hybridization demonstrated that enteric neurons express B-50. These findings are consistent with a role for B-50 in the documented plasticity of the adult enteric nervous system.     

Quantitative assessment of the transmission of labelled protein by the proximal and distal regions of the small intestine of young rats.

1. The plasma volume in rats aged 15-16 days was measured by dilution analysis using homologous, 125I-labelled immunoglobulin G. A mean plasma volume of 5-53 ml./100 g and a mean blood volume of 8-01 ml./100 g were obtained.2. After the injection of labelled immunoglobulin G into the heart, homogenates of various abdominal organs and of the carcass were prepared. Labelled immunoglobulin G left the vascular compartment at a rate of about 9-10%/hr over a 3 hr period. About 11% of the labelled immunoglobulin G was catabolized in 2 hr. 3. The data obtained from these studies was used to make quantitative estimates of the amount of intact immunoglobulin G transmitted from the proximal intestine and from the ileum after the intra-intestinal injection of 1000 mug of labelled immunoglobulin G.Homogenates of the experimental animals were prepared and it was estimated that over 40% of the labelled immunoglobulin G was transmitted as intact protein from the proximal intestine. The results suggest that no intact immunoglobulin G was transmitted from the ileum, but about 15% of the protein removed from the ileum was recovered in the whole body as degraded fragments precipitable with trichloroacetic acid. 4. These observations are discussed in the context of the transmission of antibodies, and their relevance to the receptor hypothesis is considered.     

Proteolytic activity during the absorption of [131I]γ-globulin in the new-born calf

1. Proteolytic activity within the small intestine of unsuckled calves less than 20 hr of age, anaesthetized with sodium pentobarbitone, has been assessed from the break-down of [(131)I]bovine serum gamma-globulin infused into the duodenum.2. Absorption of [(131)I]gamma-globulin was measured by analysis of venous blood, the levels of radioactivity attained in which were comparable with those when [(131)I]PVP K.60 (mean mol.wt. 160,000) was administered. When lymph collected from the thoracic duct during the absorption of [(131)I]gamma-globulin was injected into the femoral vein, the levels of radioactivity in the blood were close to those expected if the labelled material in the lymph had been retained within the plasma. These observations suggested that [(131)I]gamma-globulin was absorbed into the circulation of the anaesthetized young calf without significant break-down.3. Gel-filtration of lymph and plasma from calves fed [(131)I]gamma-globulin has confirmed that proteolysis before and during absorption was slight, since little (131)I labelled material of low mol.wt. was found.4. Gel-filtration of the contents of the alimentary tract from calves fed [(131)I]gamma-globulin showed that some hydrolysis occurred in the abomasum and duodenum and that this was reduced by barbiturate anaesthesia. Protein break-down in the terminal ileum was slight both in the conscious animal and in animals anaesthetized with sodium pentobarbitone.     

Regional characteristics of intestinal iron absorption in the guinea-pig.

Features of iron absorption by the upper small intestine and ileum in the adult guinea-pig have been compared. Autoradiographic methods have revealed that whilst only upper villus enterocytes in the duodenum-jejunum are involved in brush-border uptake, the entire villus epithelium in the ileum displays this function. Consistent with these results was the finding that brush-border membrane vesicles prepared from ileal mucosa demonstrated a higher capacity for iron uptake (expressed per mg protein) compared to vesicles of duodenal origin. Iron transport to blood following 30 min exposure of mucosa to 59Fe-ascorbate was some elevenfold higher in upper, compared to lower, small intestine. The relevance of these findings to our knowledge of the cellular processes involved in intestinal iron absorption and its regional localization is discussed.     

The transmission of -125-I-labelled immunoglobulin G by proximal and distal regions of the small intestine of 16-day-old rats.

1. Standard doses of -125-I-labelled rat IgG were injected into the intestinal lumen of rats aged 16 days, and their sera were sampled 2 and 3 hr later. High concentration quotients were obtained after injection into the proximal small intestime, whereas very little immunoglobulin was transmitted from doses injected into the terminal 20 cm of the small intestine. 2. The villi of the terminal 18--20 cm of the small intestine of 16-day-old rats, the region from which very little transmission of IgG occurred, were lined by tall columnar absorptive cells with very larg supra-nuclear vacuoles. The extent of the terminal intestine, in which this cell type predominated in the absorptive epithelium, varied with age. The importance of defining the precise location of the region of the intestine under examination is stressed. 3. The experimental results and the histological observations are discussed in relation to (a) the results which have been obtained using PVP, which is unsuitable as an indicator of immunoglobulin transport in the rat and (b) the histological composition of the absorptive epithelium and the maturation changes which affect the epithelium between 18 and 21 days.     

Further studies on intestinal active transport during semistarvation

1. The effect of semistarvation (sufficient to produce a loss of 18-28% of initial body weight) on the active transport of D-glucose and L-histidine by the rat, the guinea-pig and the golden hamster has been investigated by the use of sacs of everted small intestine (from upper jejunum to lower ileum).2. In the rat and the guinea-pig the dietary restriction resulted in increased active transport in all regions of the small intestine. In contrast, it caused no alteration in active transport in the hamster.3. The response in the rat was most impressive in the middle-to-lower ileum during D-glucose uptake. Whereas normal sacs from this area appeared unable to move the sugar against its concentration gradient, sacs from semistarved rats did so quite well.4. Although there was a considerable loss (24-29%) of intestinal dry weight in all three species when the food intake was reduced, shortening of the small intestine was not detectable in the guinea-pig or the hamster and was present to only a minor extent in the rat.5. Evidence is presented indicating that the enhanced active transport is not merely a reflexion of the thinning of the intestinal wall and that it occurs during complete as well as in partial starvation.     

Prenatal and postnatal development of the small intestine in the insectivore Suncus murinus

The development of the small intestine in the insectivore Suncus murinus was noted during the period from 21 days' gestation to 20 clays after birth. At 21 days of gestation, the proximal small intestine exhibited the beginning of villus formation, whereas the distal small intestine preserved the stratified epithelium. Stratified epithelium in the distal small intestine changed into a single layer by 24 days' gestation. At 26 day's gestation, each epithelial cell was immature; but by 28 days mature-looking epithelial colls were found. The shape of the villi changed from cuboid to columnar during the same period. The connective-tissue cores of the villi began to develop at 7 days after birth in the proximal small intestine and at 15 days after birth in the distal small intestine. Crypts appeared at 15 days after birth. Endocytosis of epithelial cells took place at 28 days of gestation. In the proximal small intestine, supranuclear vesicle clusters were observed first at birth; they began to decrease both in number and size at 10 days' gestation and then disappeared completely by 20 days after birth. In the distal small intestine, large supra-nuclear vacuoles were observed first at 28 days of gestation. Although these vacuoles invariably were found up to 15 days after birth, they also disappeared completely by 20 days. Epithelial cells showed a structure similar to those of the adult after weaning.     

A study of the concentrations of substance P and neurotensin in the gastrointestinal tract of various mammals

Immunoreactive substance P and neurotensin in extracts of the digestive tract of man, cat, guinea-pig, pig, rabbit, and rat were measured by radioimmunoassay using antisera directed against the C-terminal portions of the two peptides. In all species except the cat, the concentrations of substance P were highest in the small intestine, intermediate in the large intestine and lowest in the stomach and oesophagus: the digestive tract of the cat displayed a rather even distribution of substance P. As observed in the ileum of guinea-pig, rabbit, and rat, the external muscle layer including the myenteric plexus contained 2-5 times higher concentrations of substance P than the whole ileal wall, whereas the substance P concentrations in the mucosa were only about one sixth of those in the whole wall. High performance liquid chromatography of extracts of human, feline and rabbit ileum showed that all the immunoreactive substance P eluted at the positions of substance P and substance P sulfoxide. The distribution of immunoreactive neurotensin along the digestive system of all six species was very similar. The highest concentrations of neurotensin were measured in the distal part of the small intestine, whereas the large intestine, stomach and oesophagus contained only low concentrations of neurotensin relative to the concentrations in the ileum. As examined in the ileum of guinea-pig, rabbit, and rat, the mucosa exhibited 2.5-4 times higher concentrations of neurotensin than the whole ileal wall, while the concentrations of neutrotensin in the external muscle layer including the myenteric plexus were only 4-20% of those in the whole wall. High performance liquid chromatography of the immunoreactive neurotensin extracted from the cat ileum yielded a single peak corresponding to neurotensin while the immunoreactive neurotensin extracted from the ileum of man and rabbit was eluted in two peaks, 55 and 72% of the recovered immunoreactivity, respectively, corresponding to neurotensin. These findings are in line with the proposed roles of substance P in the neural, and neurotensin in the endocrine, control and maintenance of gastrointestinal motility.     

The effects of corticosterone and cortisone on the uptake of polyvinyl pyrrolidone and the transmission of immunoglobulin G by the small intestine in young rats.

1. The distribution of polyvinyl pyrrolidone along the intestinal lumen and in the intestinal wall, following oral administration to normal and corticosterone treated rats, was found to be extremely variable. Valid comparisons between the two groups of animals could not be made using this technique. 2. Three, 4 and 5 days after corticosterone treatment there was no significant change in the uptake of 125I-labelled polyvinyl pyrrolidone from standard doses injected into ligated segments of the distal small intestine; nor did the treatment induce precocious replacement of the absorptive cells in this region. Cortisone induced precocious cell replacement, a process which took up to 4 days to complete, and also led to a marked reduction in the uptake of 125I-labelled polyvinyl pyrrolidone from ligated segments of the distal intestine. 3. Three days after treatment with corticosterone (5 mg I.P. at 12 days) there was a marked reduction of labelled immunoglobulin G transport into the blood. Four and 5 days after treatment there was some recovery of the immunoglobulin G transport function. Three days after treatment with cortisone (5 mg I.P. at 12 days) there was closure of the gut to labelled immunoglobulin G. 4. The relevance of these results to antibody transmission and the termination of immunoglobulin transport is discussed.     

An immunohistochemical study of the distribution of enteric GABA-containing neurons in the rat and guinea-pig intestine

gamma-Aminobutyric acid (GABA) antiserum was applied to sections of rat and guinea-pig intestine which were subsequently processed to reveal any immunoreactivity using either fluorescence or peroxidase techniques. Immunopositive fibres were demonstrated in stomach, duodenum, ileum and colon of rat and guinea-pig intestine. Myenteric ganglia and nerve bundles in the circular muscle contained immunopositive nerve fibres, while the longitudinal muscle, submucosa and mucosa were only rarely innervated. In favourable sections, immunopositive fibres could be seen running from the myenteric plexus into the circular muscle, thus suggesting that the GABA-immunopositive nerves in the circular muscle originate from neurons in the myenteric plexus. In both rat and guinea-pig, immunoreactive nerve cell bodies were most numerous in the myenteric plexus of the colon. In the rat, immunopositive fibres in the circular muscle were most abundant in the ileum, whereas in the guinea-pig it was the colon circular muscle that was most richly innervated. The results demonstrate that neurons which show GABA immunoreactivity are present along the length of the gastrointestinal tract. Their distribution in both myenteric ganglia and circular muscle is heterogeneous both within and between the two species studied. It is probable that this heterogeneity reflects the diversity and specificity of function of this class of enteric neurons.     

Fractionation studies on the absorption of labelled immunoglobulin G by the gut of young rats.

1. Centrifugation in density gradients was used to study the fragments produced during intraluminal and intracellular digestion, after the injection of 125I-labelled immunoglobulin G (IgG) into different regions of the small intestine of 14 to 15-day-old (pre-closure) and 24-day-old (post-closure/ rats. 2. After injection into the proximal small intestine and into the ileum of pre-closure animals, the bulk of the radioactivity recorded for gut washes and gut homogenates was located at 4S-7S. The serum from animals which had received injections into the proximal small intestine had high radioactivity and one peak at 7S; the serum from animals which had received injections into the ileum had low radioactivity and no activity in the 7S region. 3. After injection into the proximal small intestine of post-closure animals, the bulk of the radioactivity recorded for gut wash samples was located at 3-5S--5S. Gut homogenates had peak activity at 2-5S--4S. Thus large molecular weight products can be absorbed by the proximal enterocytes of post-closure rats and degraded. The sera of these animals had low radioactivity. 4. After injection into the distal small intestine of post-closure animals, the bulk of the radioactivity recorded for gut wash and gut homogenate samples was located at 4S-7S and in this respect the radioactivity plots resembled those for (2) above. Serum radioactivity was low. 5. The effect of precipitation with trichloroacetic acid and incubation with specific antiserum upon the radioactivity of gut washes, gut homogenates and serum samples was recorded. 6. The relevance of these findings to studies on the transmission of protein by the rat small intestine is discussed.