This study is the first to document the spatial and temporal lumenal concentrations of choline in the intes¬tinal lumen of the rat, and shows a general lack of effect of parasitism by the cestode H. diminuta on the free choline gradients during the early stages of feeding, but does show a more marked effect on free intestinal lumenal choline concentrations in trie "unfed rat.
The physiological free choline concentrations, disre¬garding time of feeding, ranged from a mean of almost 3 mM in the first intestinal segment, which corresponds to the ciupdenum, to as low-as 21 //M in the posterior ileum of the uninfected rat. However, the concentra¬tions were highly variable in the first few segments which represent the duodenum and anterior jejunum. The reason,for this enormous Variation is not clear, but may reflect differences in stomach emptying rates. Thus the contents of the duodenal lumena, although similar in volume, may have contained variations in acid chyme content. Further, a Variable content of acid chyme released into the duodenum and diluted by the endogenous secretions in the duodenum may produce highly variable concentrations in free choline in the anterior intestinal lumen. There appear to be no studies on the effect of parasitism on the rate of stomach emptying in rats.
In unfed rats, the lumenal choline concentrations were frequently significantly higher than those in the uninfected rat. In contrast, wtien rats commenced feed¬ing, where infected rats commenced feeding at the same time as uninfected rats, the concentrations of free choline in the intestinal lumena were but little influ¬enced in the first 6 h after feeding, or by infection with H. diminuta. However, by 9 h post feeding, the choline levels in the posterior ileum were significantly elevated, and by 12 h the profile resembled that seen in unfed uninfected or infected rats. These data collectively sug¬gest that infection has little effect on the dynamics of the intestinal lumenal-choline concentrations during the feeding cycle, but that some mechanism exists to elevate choline levels in the latter part of the feeding state and during the unfed state. During the latter part of the fed state, and during the unfed state, the worms may either significantly increase free choline concentrations, per¬haps by enhanced hydrolysis of choline containing compounds or inhibit uptake of choline by the intestine through acidification or, as a result of a decrease in the microbiota significantly more free choline is available to both the rat and the worms. The rapid decrease in choline concentrations seen in segments 3 and 4, the jejunum, of uninfected rats may indicate an area for choline absorption, which would be consistent with the major site of choline absorption being the jejunum in vertebrates However, this decrease in choline concentration may also be a reflec¬tion of dilution of exogenous free choline with endoge¬nous secretions. For example, the duodenum of the rat receives pancreatic juice and bile. The latter contains large quantities of esterified choline, mostly in the form of phosphatidylcholine. Some of this phosphatidyl¬choline, along with dietary phosphatidylcholine may be rapidly degraded to produce lysophosphatidylcholine and eventually glycerophosphorylcholine but little free choline is released. This is unlike the situation in a ruminant, such as sheep, where phosphatidylcholine in the ingesta is rapidly degraded by rumen-dwelling mi¬croorganisms to liberate free choline, which is then rapidly oxidized by microorganisms. Thus most of the free choline observed in the intestinal lumen of the rat is likely of dietary origin.
The high concentrations of free choline in the intesti¬nal lumena of infected rats indicate that, given a worm tissue choline concentration of 20 yuM , choline may rapidly enter the worms by sodium-dependent and sodium-independent transport down both a concentra¬tion and electrochemical gradient , where it may be used for acetylcholine synthesis or phospholipid synthesis . Even in the posterior small intestine, the lumenal concentrations of choline are equal to or higher than those in the worm tissues , suggesting that choline entry into the worm tissues can continue down a concentration gradient throughout all regions of the rat small intestine. Furthermore, the choline concentration in rat blood varies from 5.1 to 24.3 μM , which are, at the higher range, similar to the concentrations of choline observed in the small intesti¬nal lumen. This may suggest that, like the brain , choline uptake and release from the posterior small intestine is balanced by the concentration of choline in the blood. Thus the availability of choline in the rat intestinal lumen is not likely to be a limiting factor in worm growth.
In the rat, 18-54% of dietary choline is converted to tissue phosphatidylcholine , although as much as 50% of ingested choline may be metabolized to betaine , However, it is not known to what extent choline is oxidized in the intestinal lumen of the infected rat by the microflora and fauna, which are known to be changed qualitatively and reduced quantitatively as a result of the infection . It is possible that a decrease in choline loss to microflora and fauna as a result of infection, is partially offset by the uptake of choline by the worms, resulting in the observed small or absent differences in intestinal lumenal choline concentrations between infected and uninfected rats during the early stages of the feeding state. Further, there were signifi¬cant elevations in choline concentrations in infected rats in the unfed state, which may indicate that the worms enhance the lumenal concentrations of free choline, wither by effects on the rat host, or effects on the intestinal microflora and fauna. Moreover, there are no studies to determine if H. diminuta may have a signifi¬cant effect of the dynamics of production of choline from lysophosphatidylcholine, glycerophosphoryl-choline or phosphorylcholine from lumenal phos¬phatidylcholine, or on choline transport by the rat host in the unfed state or during feeding.
The worm biomass distribution was changed as a result of feeding. There was a small shift toward the duodenum soon after feeding, followed subsequently by
a more posteriad shift. This same situation has been documented in many other laboratories where follow¬ing feeding, the worms migrated toward the duodenum, followed by a posteriad migration. However, during the feeding state, the presence of the worm biomass in the segments of the intestine had little or no effect on the lumenal choline concentrations. This is unlike the situation seen with carbohydrate, amino acid and sero¬tonin gradients in which infection of the rat resulted in pronounced changes in the nutritional gradients and serotonin gradients. This observation supports our hypothesis that availability of choline is not likely a limiting factor in worm growth.