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PubMed1993

[Regulation of cholesterol absorption in human and rat small intestine epithelial cells].

Cholesterol absorption in human small intestine organ culture and rat small intestine epithelial cell culture IRD-98 has been studied using [14C] cholesterol, [3H] cholesterol and [14C] sitosterol. It has been found that cholesterol absorption is a dose- and time-dependent process, while sitosterol absorption is not and makes up to about 25% of the total cholesterol absorption. Cholesterol absorption appeared to be a specific process. The endocytosis inhibitor monensin decreased specific cholesterol absorption by 37%. Cholesterol absorption was examined under different conditions influencing cholesterol metabolism in the cell. Loading of IRD-98 cells with non-lipoprotein cholesterol caused a dose-dependent decrease of cholesterol absorption. The inhibitor of acyl coenzyme A:cholesterol acyl transferase (ACAT), compound Sandoz 58-035, had a similar effect on cholesterol absorption. Lovastatin, an inhibitor of 3-hydroxymethyl-3-glutaryl coenzyme A (HMG-CoA) reductase, stimulated cholesterol absorption in a dose-dependent manner. Loading of cells with cholesterol, lovastatin and Sandoz 58-035 had no effect on sitosterol absorption. The possibility has been demonstrated of using human small intestine organ culture and rat small intestine epithelial cell culture IRD-98 as models for studying cholesterol absorption.

Adolescent↗
PubMed1990

Aldosterone and PCO2 enhance K-dependent chloride absorption in rat distal colon.

We have previously demonstrated that, in the absence of Na+ in vitro, the rate of colonic K+ absorption is increased by increasing PCO2. Chronic secondary hyperaldosteronism induced by dietary Na-depletion further stimulated K+ absorption under these conditions. Because the observed increments in CO2-dependent K+ absorption were not accompanied by corresponding changes in short-circuit current, macroscopic electroneutrality must have been maintained either by anion absorption or by cation secretion. Colonic Cl- absorption is known to respond to increased PCO2 both in vivo and in vitro, but its response under Na-free conditions and the relationship to K+ absorption have not been examined. To determine the relationship of Cl- absorption to K+, we measured unidirectional fluxes of 36Cl and the response to PCO2 in voltage-clamped segments of rat distal colon. Our findings indicate that the rate of Cl- absorption is increased by increasing CO2, both in the presence and absence of Na+. Under Na-free conditions, Cl- absorption is inhibited by acetazolamide and by the absence of K+;K+ absorption (86Rb or 42K flux) is inhibited in a reciprocal fashion by the absence of Cl-. The rates of K+ and Cl- absorption are similar in controls and after secondary hyperaldosteronism due to a Na-deficient diet. These findings suggest that K- and Cl- absorption are closely coupled under Na-free conditions, most likely due to the operation of parallel, aldosterone-responsive H(+)-K+ and Cl(-)-HCO3- exchange pathways.

Acetazolamide↗
PubMed1963

Cation-anion balance during potassium and sodium absorption by barley roots.

Steady-state rates of potassium ion and sodium ion absorption by excised barley roots accompanied by various anions were compared with the rates of anion absorption and the concomitant H(+) and base release by the roots. The cation absorption rates were found to be independent of the identities, concentrations, and rates of absorption of the anions of the external solution, including bicarbonate. Absorption of the anion of the salt plus bicarbonate could not account for the cation absorption. H(+) is released during cation absorption and base during anion absorption. The magnitude by which one or the other predominates depends on the relative rates of anion and cation absorption under various conditions of pH, cation and anion concentration, and inhibitor concentrations. The conclusion is that potassium and sodium ions are absorbed independently of the anions of the absorption solution in exchange for H(+), while anions are exchanged for a base. The H(+) release reflects a specificity between K(+) and Na(+) absorption such that it appears to be H(+) exchanged in the specific rate-limiting reactions of the cation absorption.

Anions↗
PubMed2007

Markers of absorption and synthesis of cholesterol in men with type 1 diabetes.

BACKGROUND AND METHODS: Serum cholestanol and plant sterol ratios to cholesterol, surrogate markers of cholesterol absorption, are assumed to be high in type 1 diabetes (T1D), and the ratios of cholesterol precursor sterols (markers of synthesis) are assumed to be low reflecting downregulated cholesterol synthesis. To this end, we measured serum sterols with gas-liquid-chromatography in 56 men with T1D and in 18 controls to evaluate cholesterol metabolism. Subjects were categorised into tertiles by the cholestanol to cholesterol ratio of controls indicating low to high absorption of cholesterol. RESULTS: The ratios of the synthesis markers were negatively related to the absorption markers in controls, but less consistently in T1D. The absorption markers were positively related to each other, but interrelation of the synthesis markers was less consistent in T1D. In the low absorbers the absorption markers were higher in T1D than in controls (e.g. sitosterol ratio 173 +/- 9 in T1D vs 135 +/- 11 10(2) x mmol/mol of cholesterol in controls, p < 0.05). In the high absorbers, the absorption markers were similar in T1D and controls, but the synthesis markers were higher in T1D than in controls (e.g. lathosterol ratio 154 +/- 10 in T1D vs 120 +/- 5 10(2) x mmol/mol of cholesterol in controls, p < 0.05). CONCLUSIONS: Absorption and synthesis of cholesterol are less closely related to each other in T1D than in controls, but the markers of cholesterol absorption are interrelated also in T1D. Absorption of cholesterol is higher in T1D than in controls within the range of low absorption, but similar in those with relatively high cholesterol absorption.

Adult↗
PubMed1986

Allopurinol absorption from different sites of the rat gastrointestinal tract.

Allopurinol exhibits good bioavailability (78-90%) after administration of oral dosage forms to humans and rabbits; however, it is not absorbed rectally from any of the dosage forms to any significant extent. Oral administration of allopurinol in a polyethylene glycol suspension, to which allopurinol may be reversibly complexed, to rabbits has been shown to produce erratic and poor absorption of allopurinol. This suggests the possibility of differential absorption of allopurinol from various sites of the GI tract. The mechanism of allopurinol absorption was investigated in rats using the in situ Levine technique. The allopurinol absorption rate was 0.56 +/- 0.10 microgram/min/cm from the upper portion of the small intestine and was 0.48 +/- 0.12 microgram/min/cm from the midgut. The absorption from the lower portion of the small intestine was 0.33 +/- 0.14 microgram/min/cm and from the upper and lower large intestine segments was negligible (0.04 +/- 0.06 microgram/min/cm). The normalization of these absorption rates for surface area yielded flux values (normalized absorption rate as microgram/min/cm2) with significant differences in permeability between small and large intestine for allopurinol. The allopurinol absorption rate increased with increases in the dose, and there was a linear relationship between dose and absorption rate. Thus, allopurinol absorption, although specific to particular sites, is not dose dependent in the dose range from 0.25 to 2.5 mg/mL. Differences in the rates of absorption may be due to anatomical differences of the various parts of the GI tract or due to physicochemical properties of the drug itself.

Allopurinol↗
PubMed1978

Diurnal rhythmicity of absorption of a lipid compound (vitamin K-1) in vivo in the rat.

The possibility of rhythmicity in the intestinal absorption of lipids was explored by assessing the absorption of vitamin K-1 by the unanesthetized rat at 6 PM, 12 and 6 AM, and 12 PM. A marked variability in the absorption rate of vitamin K-1 was found throughout the 18-hr period. The highest rates of absorption occurred at midnight (139.8 +/- .22 and 134.4 +/- 9.1 pmol/min/10 cm of jejunum and ileum, respectively). The lowest rates of absorption occurred at 6 AM (54.5 +/- 1 and 81.4 +/- 7.4 pmol/min/10 cm of jejunum and ileum, respectively). Absorption rates at noon were not different from absorption at 6 AM but an initial increase in absorption was noted at 6 PM. Synchronization of the absorptive rate with time is most likely related to the time of feeding and not to changes in the pattern of illumination. The possibility of marked diurnal variability in the absorption rate should be considered in the design and execution of intestinal absorption experiments.

Animals↗
PubMed1994

Effect of alpha 1-adrenergic blockade on canine ileal water, electrolyte, and glucose absorption.

Meal ingestion stimulates an increase in small intestinal water and electrolyte absorption. Endogenous norepinephrine may at least partially mediate this meal-stimulated proabsorptive response. Luminally administered alpha 1-adrenergic agonists such as norepinephrine and phenylephrine cause significant small bowel absorption, which can be prevented by the selective alpha 1-adrenergic antagonist terazosin. This study tested two hypotheses: (1) a meal stimulates ileal water, electrolyte, and glucose absorption; and (2) meal-stimulated ileal absorption is mediated via alpha 1-adrenergic receptor activation. Absorption studies (N = 27) were performed on dogs with 25-cm ileal Thirty-Vella fistulas (TVF). Perfusion with [14C]PEG was used to calculate absorption of water, electrolytes, and glucose from the TVF. Three groups were randomly studied over 4 hr: (1) terazosin alone, (2) meal alone, and (3) terazosin plus meal. Terazosin (10(-4) M) was administered to the TVF in groups 1 and 3 following the first hour. A 480-kcal mixed canine meal was ingested at the end of the second hour in groups 2 and 3. Ileal water, electrolyte, and glucose absorption increased significantly in response to meal ingestion (P < 0.05). Luminal terazosin did not significantly alter basal or meal-stimulated ileal absorption. In conclusion, meal ingestion stimulates ileal absorption of water, electrolytes, and glucose. Neither basal nor meal-stimulated ileal absorption is altered by alpha 1-adrenergic receptor blockade. These data suggest that nonadrenergic neural pathways or humoral factors are the likely mediators of meal-induced intestinal absorption.

Adrenergic alpha-Antagonists↗
PubMed1992

Nonlinearity of amoxicillin absorption kinetics in human.

Specialised gastrointestinal absorption of amoxicillin has been suggested in man and has been demonstrated in animals. In order to study the rate and extent of amoxicillin absorption, six healthy subjects were given 500 mg IV and two oral doses (500 mg and 3 g as a suspension). Absorption kinetics was analysed by compartmental modelling, noncompartmental methods and by calculation of absorption rates using deconvolution. Dose-dependency of the extent of amoxicillin absorption was observed, with a lower than expected mean maximum plasma concentration (49%), and fraction of the dose absorbed (39%) after the 3 g dose calculated from the 500 mg dose, assuming kinetic linearity. Zero-order kinetics of absorption was apparent in some subjects after the 500 mg dose, both from model fitting and absorption rate profile. However, no pattern consistent with pure first-order or zero-order absorption was observed after both oral doses in any individual. The dose-dependency of amoxicillin absorption was confirmed by a trend to an increased time of absorption for the high dose. The results show the variable nature and nonlinearity of the gastrointestinal absorption of amoxicillin and indicate the involvement of a number of factors, in addition to simple diffusion.

Amoxicillin↗
PubMed1980

25-hydroxy vitamin D absorption test in patients with gastrointestinal disorders.

To evaluate the relationships of a 25-hydroxy vitamin D absorption test to intestinal fat absorption and to the absorption of radioactively labeled vitamin D and 25-hydroxy vitamin D, an investigation was undertaken in 19 patients with gastrointestinal disorders. A correlation was noted between the results of the 25-hydroxy vitamin D absorption test and baseline 25-hydroxy vitamin D levels. No correlation was found between results of the 25-hydroxy vitamin D absorption test and quantitative fecal fat excretion. Peak values of the 25-hydroxy vitamin D absorption test correlated with net absorption of 14C vitamin D. No correlation existed between the values obtained in the 25-hydroxy vitamin D absorption test and 3H-25-OH D absorption. These studies indicate that the 25-hydroxy vitamin D absorption test probably does not serve as an effective screening test for intestinal fat malabsorption. The results of the test probably most accurately reflect the body stores of vitamin D at the time of testing, but there appears to be little advantage to performing a 25-hydroxy vitamin D absorption test in lieu of a single determination of the serum level of 25-hydroxy vitamin D as a method of evaluating vitamin D nutritional status.

Carbon Radioisotopes↗
PubMed1987

Central administration of benzodiazepines alters water absorption by the rat ileum in vivo.

Two types of benzodiazepine receptors have been identified in the central nervous system. The aim of these experiments was to determine if ligands for these receptors alter basal water absorption by rat ileum in vivo after central administration. Specifically, the effects on net water flux of the systemic and central administration of diazepam and the central administration of RO 5-4864, a "peripheral" receptor agonist, and of the "central" receptor agonists clonazepam and lorazepam were determined. Diazepam increased absorption at 4.3 mg/250 g body wt i.p. but not at 430 micrograms/250 g body wt. Intracerebroventricular diazepam (28 micrograms) increased water absorption. Larger doses had a greater effect. Intracerebroventricular RO 5-4864 (100 micrograms) increased net water absorption; intracerebroventricular lorazepam (50 or 100 micrograms) or clonazepam (100 micrograms) reduced basal water absorption. Systemic atropine (2 mg/kg i.v.) abolished the effect of lorazepam (100 micrograms i.c.v.). To evaluate the possibility that diazepam and RO 5-4864 have effects similar to those of calcium channel antagonists, nifedipine, nitrendipine, and diltiazem were administered intracerebroventricularly. The dihydropyridine calcium channel antagonists nifedipine and nitrendipine increased basal water absorption. Diltiazem, a benzothiazepine compound, did not alter basal water absorption. We conclude that the binding of benzodiazepine agonists to receptors located in the central nervous system alters net water absorption by the rat ileum. Agonists of the central benzodiazepine receptor reduce basal water absorption via a cholinergic neural pathway. Peripheral agonists increase net water absorption. In this model, diazepam behaves as a peripheral receptor agonist. This study provides further evidence of a role for the central nervous system in the regulation of intestinal absorption of water and ions.

Animals↗
PubMed1992

Sugar absorption by the biliary ductular epithelium of the rat: evidence for two transport systems.

Sugar absorption by the biliary ductular epithelium under steady-state conditions was examined using isolated perfused rat liver. The test sugar and mannitol (as a putative marker of paracellular entry) were added to the glucose-free recirculating perfusate each at a concentration of 5 mmol/L, and apparent active biliary ductular absorption equated with the change in concentration of the test sugar relative to that of mannitol. A metabolizable hexose (D-glucose), pentose (D-xylose), and three nonmetabolizable hexoses (alpha-methyl-glucoside, 3-o-methyl-glucose, and L-glucose) were used. All five monosaccharides were well absorbed at constant rates for 2 hours with apparent rates of absorption (mumol.kg body weight-1.min-1, mean +/- SE) of D-glucose, 0.24 +/- 0.01; L-glucose, 0.20 +/- 0.02; 3-o-methyl-glucose, 0.19 +/- 0.02; alpha-methyl-glucoside, 0.16 +/- 0.03; and D-xylose, 0.10 +/- 0.04. The addition of phloridzin to the perfusate inhibited D-glucose absorption in part but did not inhibit L-glucose absorption. When perfusate Na+ was replaced by N-methylglucamine, the bile-plasma ratio of mannitol remained unchanged, as did the apparent absorption rate of D-glucose and 3-o-methyl-glucose. In contrast, absorption of L-glucose and alpha-methyl-D-glucoside gradually ceased. The addition of 15 mmol/L glucose to the perfusate caused decreased bile flow and increased taurocholate concentration in bile, suggesting that glucose absorption by the biliary ductules induced water reabsorption. It is concluded that sugars are absorbed by the biliary ductular system by Na(+)-dependent and Na(+)-independent transport systems, the substrate affinities of which differ from those reported for apical membrane hexose transport systems in renal tubular and intestinal epithelia. Ductular absorption of solutes such as glucose that enter bile passively may have biological use, because ductular absorption decreases the concentration of substrates for bacterial growth in gallbladder bile. On the other hand, ductular absorption of solutes induces reabsorption of biliary water, resulting in decreased bile flow; this might contribute to cholestasis during prolonged hyperalimentation with solutions containing glucose.

Absorption↗
PubMed1992

Mucosal ouabain and Na+ inhibit active Rb+(K+) absorption in normal and sodium-depleted rat distal colon.

To determine the effect of mucosal sodium and mucosal ouabain on active Rb+(K+) absorption, unidirectional and net 86Rb+ fluxes were measured under voltage-clamp conditions in the distal colon of normal and sodium-depleted rats. The role of mucosal sodium (independent of serosal sodium) was evaluated in a model of Rb+(K+) absorption in which serosal ouabain markedly enhanced active Rb+(K+) absorption. In normal rats, mucosal sodium was a competitive inhibitor of Rb+(K+) absorption, and Rb+(K+) absorption consisted of a mucosal sodium-sensitive component and a mucosal sodium-insensitive component. Further, mucosal ouabain almost completely inhibited the mucosal sodium-insensitive component but did not affect the mucosal sodium-sensitive component. In sodium-depleted rats, both mucosal sodium-sensitive and mucosal sodium-insensitive fractions of Rb+(K+) absorption were also identified. Aldosterone markedly stimulated the mucosal sodium-sensitive component (1.68 +/- 0.15 vs. 0.60 +/- 0.10 muEq.h-1.cm-2) but not the sodium-insensitive component (0.88 +/- 0.09 vs. 0.64 +/- 0.06 muEq.h-1.cm-2) component of Rb+(K+) absorption; however, in contrast to normal animals, mucosal sodium in sodium-depleted animals was a noncompetitive inhibitor of Rb+(K+) absorption. The mucosal sodium-insensitive component of Rb+(K+) absorption in sodium-depleted animals was substantially inhibited by mucosal ouabain, but the mucosal sodium-sensitive component, unlike that in normal animals, was partially inhibited by mucosal ouabain. These studies indicate that the characteristics of the Rb+(K+) absorptive process in sodium-depleted animals differ significantly from those present in normal animals, suggesting that aldosterone induces an Rb+(K+) absorptive mechanism not present in normal animals.

Animals↗
PubMed1990

The effect of calcium on gallbladder absorption.

The absorption of water and electrolytes is an important physiologic function of the gallbladder which is altered during gallstone formation. Extracellular calcium and calcium channel antagonists are known to affect intestinal absorption, yet their effect on gallbladder absorption is less well defined. We, therefore, tested the hypothesis that changes in extracellular calcium or in calcium channels would alter gallbladder absorption. New Zealand white rabbit gallbladders were removed, filled with a modified Krebs buffer (Ca2+ = 0.7 mM), and suspended in an oxygenated bath of the same buffer. Water absorption was determined gravimetrically by obtaining serial gallbladder weights at 10-min intervals. After a 40-min control period, the serosal bathing solution was changed to one of four experimental solutions (n = 6 for each group): Ca2+ = 0.25, 0.7, or 1.2 mM or Ca2+ = 0.7 mM plus 0.1 mM verapamil. Absorption was determined during an 80-min experimental period with results expressed as the percentage change in gallbladder absorption compared to that of the control period. The 0.25, 0.7, and 1.2 mM Ca2+ groups did not show a significant change in absorption rate from their respective control rates. However, the verapamil group did demonstrate a significant (P less than 0.05) decrease in absorption rate of -69 +/- 8% by the end of the experimental period. These data demonstrate that verapamil inhibits gallbladder absorption while changes in serosal calcium concentration have no effect. We conclude that calcium channels and intracellular calcium may play an important role in modulating gallbladder absorption.

Absorption↗
PubMed2006

Postprandial augmentation of absorption of water and electrolytes in jejunum is neurally modulated: implications for segmental small bowel transplantation.

Postprandial augmentation of absorption of water and electrolytes is believed to occur in the jejunum. Neural mechanisms of control, however, have not been studied in the in situ jejunum or in the transplanted bowel. The aim of this study was to determine if postprandial augmentation of absorption occurs in the in situ jejunum and to evaluate neural mechanisms controlling postprandial jejunal absorption. Based on our previous work, we hypothesized that postprandial augmentation of absorption does not occur in the jejunum in situ and that extrinsic denervation of the jejunum is associated with decreased postprandial absorption. Absorption was studied in an 80 cm, in situ jejunal segment in six dogs by using an isosmolar electrolyte solution alone, or with 80 mmol/L glucose before and after jejunal transection to disrupt intrinsic neural continuity of the study segment with the remaining gut. Net absorptive fluxes of water and electrolytes were measured in the fasted state and after a 400-kcal meal. Another six dogs were studied 3 weeks after our validated model of extrinsic denervation of jejunoileum; identical fasting and postprandial absorptive states were evaluated. Postprandial augmentation of absorption of water and electrolytes did occur in the jejunum (P < 0.03) both in the absence and in the presence of intraluminal glucose. After intrinsic neural transection or extrinsic denervation, no postprandial augmentation of absorption occurred, with or without glucose. Postprandial augmentation of absorption of water and electrolytes occurs in the in situ jejunum. Disrupting intrinsic neural continuity or extrinsic denervation (as after intestinal transplantation) abolishes postprandial augmentation.

Anastomosis, Surgical↗
PubMed2005

Epinephrine is an enhancer of rat intestinal absorption.

Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs.

Animals↗
PubMed2004

Absorption of D(+)-xylose, cobalamin, and folic acid after autologic-allotopic ileum mucosa transplantation in beagles.

BACKGROUND/PURPOSE: Ileum mucosa transplantation in a demucosed colon coat was developed as a new method for small bowel elongation. In an animal model, the authors investigated the absorptive capacity of the transplanted mucosa for D(+)-xylose, cobalamin (vitamin B12), and folic acid. METHODS: Ileum mucosa was transplanted in a vascularized demucosed segment of transverse colon in 18 beagle dogs. The colon coat-ileum mucosa complex then was integrated in the ileal continuity. Absorptive capacity for D(+)-xylose, cobalamin, and folic acid was measured before and 4 weeks after transplantation. The results were compared and analyzed with the Students' t test for matched pairs. All determined blood values with P values less than.05 were considered to show a significant reduction in the absorptive capacity of the transplanted ileum mucosa. RESULTS: Fifteen minutes after application there was no significant difference in the absorption of D(+)-Xylose and cobalamin between normal and transplanted ileum mucosa (P >.1). Absorption of folic acid in the transplanted segment was lower but not significant (P <.1). After 30 minutes D(+)-xylose and cobalamin again showed no difference between the absorptive capacity of normal and transplanted ileum mucosa (P >.1), whereas folic acid continued with the tendency toward an impaired absorption (P <.1). However, after 60 minutes, the difference of the absorptive capacity of the transplanted ileum mucosa was significant (P <.05) for folic acid. D(+)-xylose showed a tendency for an impaired uptake (P <.1), whereas absorption of cobalamin did not differ significantly after transplantation (P >.1). CONCLUSIONS: Experimental autologic-allotopic ileum mucosa transplantation is a feasible new method for small bowel elongation in an animal model. Examination of the absorptive capacity of the transplanted ileum mucosa showed a normal uptake for cobalamin, while there was an impaired absorption of D(+)-xylose and folic acid.

Animals↗
PubMed2006

Physiological and therapeutic factors affecting cholesterol metabolism: does a reciprocal relationship between cholesterol absorption and synthesis really exist?

Cholesterol absorption and synthesis contribute to maintaining cholesterol homeostasis. Several physiological and therapeutic factors affect cholesterol homeostasis, including: genetics, circadian rhythm, body weight, plant sterols, ezetimibe, and statin therapy. The present objective is to determine the main vector, i.e. cholesterol absorption or synthesis, affected by each of these factors, and to examine whether an alteration in one vector is linked to a reciprocal change in the other. Current techniques used to assess cholesterol absorption and synthesis are also reviewed. Review of physiological factors affecting cholesterol metabolism suggest a reciprocal relationship between these two vectors. Carriers of the E2 isoform of apolipoprotein E and ATP binding cassette (ABC) G8 19H (exon 1 mutation) show a decrease in cholesterol absorption accompanied by a corresponding increase in synthesis. Circadian rhythm affects cholesterol synthesis, however, its effect on absorption has yet to be established. Obese subjects show an increase in cholesterol synthesis with a subsequent decrease in cholesterol absorption. Weight loss down regulates cholesterol synthesis, but has little or no effect on absorption. In the case of therapeutic factors, plant sterols and stanols inhibit cholesterol absorption, which results in a compensatory increase in synthesis. Ezetimibe also decreases intestinal absorption, while reciprocally increasing synthesis. Statin therapy down regulates synthesis, which is accompanied by a rise in absorption. These findings suggest that a change in one vector, fairly consistently, results in a compensatory and opposing change in the other. An understanding of this reciprocal relationship between cholesterol absorption and synthesis may allow for the development of more effective interventions for dyslipidemic disorders.

Animals↗
PubMed2000

Downregulation of ileal bile acid absorption in bile-duct-ligated rats.

BACKGROUND/AIMS: Accumulation of toxic bile acids in cholestasis contributes to liver injury and depends on their synthesis, secretion and intestinal absorption. In the present study, we investigated the effect of cholestasis on the active ileal absorption of bile acids in vivo and the adaptation of transporters involved in ileal bile acid absorption. METHODS: Male Wistar rats underwent ligation of the common bile duct or biliary diversion. Sham-operated rats served as controls. Active ileal bile acid absorption of taurocholate was measured by an intestinal perfusion technique. Transporter mRNA levels of the Na+/bile acid cotransporting protein (IBAT), ileal lipid binding protein (ILBP) and organic anion transporter subtype 3 (Oatp3) and protein expression of IBAT and ILBP were determined in the distal ileum. RESULTS: After bile duct ligation the intestinal absorption rates of taurocholate were lower (p<0.05) and after biliary diversion absorption rates were higher compared to sham-operated animals (p<0.05). The absorption rates were inversely correlated to serum bile acid concentrations. Levels of IBAT-, ILBP- and Oatp3- mRNA were not different between the groups. However, in cholestatic rats, the expression of the 99-kDa dimer of IBAT was decreased compared to controls (p<0.05), whereas the 46-kDa monomeric protein of IBAT and the expression of ILBP was unchanged. After biliary diversion a similar pattern of protein expression was observed, despite an increased absorption rate. CONCLUSIONS: Cholestasis leads to a decreased active ileal absorption of taurocholate. The changes in protein expression may not account for the different absorption rates. The intestinal absorption of bile acids seems to be regulated by their systemic concentration.

Animals↗