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The use of buccal partitioning as a model of drug absorption interactions.

Bioavailability describes both the rate and extent of drug absorption. The buccal absorption technique is a useful method for the examination of changed extent of drug absorption resulting from drug absorption interactions. The present work examined the usefulness of drug recovery profiles (after buccal absorption) in evaluating the rate of drug absorption. Recovery data, in the case of propranolol, did not change markedly after marked changes in the drug absorption rate, indicating that recovery profiles are a poor monitoring tool for changed absorption rates. The rate of drug absorption can be found using the buccal absorption method; however, this involves several different experiments on different days and, also, data must be found by measuring the drug in the absorption solution which also contains the interactant. The latter agent may interfere with drug assay procedures. The present work involved the model drug propranolol. Other drugs perhaps may behave differently.

Absorption↗

Endogenous prolactin modulated the calcium absorption in the jejunum of suckling rats.

Prolactin has been reported to stimulate intestinal calcium absorption in young and mature, but not aging rats. The present study was performed on suckling rats to elucidate the actions of endogenous prolactin on calcium absorption in various intestinal segments. Before measuring the calcium fluxes, 9-day-old rats were administered for 7 days with 0.9% NaCl, s.c. (control), 3 mg/kg bromocriptine, i.p., twice daily to abolish secretion of endogenous prolactin, or bromocriptine plus exogenous 2.5 mg/kg prolactin, s.c. Thereafter, the 16-day-old rats were experimented upon by instilling the 45Ca-containing solution into the intestinal segments. The results showed that, under a physiological condition, the jejunum had the highest rate of calcium absorption compared with other segments (1.4 +/- 0.35 micromol.h-1.cm-1, p < 0.05). The duodenum and ileum also manifested calcium absorption, whereas the colon showed calcium secretion. Lack of endogenous prolactin decreased lumen-to-plasma and net calcium fluxes in jejunum from 2.07 +/- 0.31 to 1.19 +/- 0.12 and 1.40 +/- 0.35 to 0.88 +/- 0.18 micromol.h-1.cm-1 (p < 0.05), respectively, and exogenous prolactin restored the jejunal calcium absorption to the control value. Endogenous prolactin also had an effect on the duodenum but, in this case, exogenous prolactin did not reverse the effect of bromocriptine. However, neither ileal nor colonic calcium fluxes were influenced by prolactin. Because luminal sodium concentration has been demonstrated to affect calcium absorption in mature rats, the effect of varying luminal sodium concentrations on calcium fluxes in suckling rats was evaluated. The jejunum was used due to its highest rate of calcium absorption. After filling the jejunal segments with 124 (control), 80, 40 mmol/L Na+-containing or Na+-free solution, increases in calcium absorption were found to be inversely related to luminal sodium concentrations in both control and bromocriptine-treated rats. The plasma concentration of 45Ca under luminal sodium free condition was also higher than that of the control condition (2.26% +/- 0.07% vs. 2.01% +/- 0.09% administered dose, p < 0.05). However, 3H-mannitol, a marker of the widening of tight junction that was introduced into the lumen, had a stable level in the plasma during an increase in plasma 45Ca, suggesting that the widening of tight junction was not required for enhanced calcium absorption. In conclusion, calcium absorption in suckling rats was of the highest rate in the jejunum where endogenous prolactin modulated calcium absorption without increasing the paracellular transport of mannitol.

Algorithms↗

Suppression of coupled Na-Cl absorption by aldosterone and dexamethasone in rat distal colon in vitro.

Basal Na absorption in the rat colon is coupled to that of Cl in an electroneutral fashion. We previously determined that aldosterone or dexamethasone induces amiloride-sensitive mucosal-to-serosal Na flux approximately equal to the amiloride-sensitive short-circuit current in rat distal colon in vitro. However, the effect of these steroids on coupled Na-Cl absorption was not examined. For this purpose, we determined the unidirectional flux of Na and Cl in voltage-clamped distal colon segments from rats treated with aldosterone or dexamethasone. Amiloride was used as a probe for conductive Na absorption, and acetazolamide and Cl-free solutions were used as probes for coupled Na-Cl absorption. Our results indicate that the nature of colonic Na absorption is markedly changed after treatment with these steroids. In contrast to findings in the untreated rat, colonic Na absorption after treatment with aldosterone or dexamethasone was largely independent of the presence of Cl. Net Cl absorption and acetazolamide sensitivity were both greatly diminished. Thus, aldosterone and dexamethasone have multiple effects on Na transport in rat distal colon. In addition to the stimulation of conductive Na absorption by aldosterone, an effect well described in other epithelia, there is marked suppression of coupled Na-Cl absorption. Dexamethasone was less effective in suppressing Cl absorption but equally effective in stimulating conductive Na absorption. These steroid effects were greater in the terminal 1-2 cm of the rat colon.

Acetazolamide↗

Inhibition of bicarbonate absorption by peptide hormones and cyclic adenosine monophosphate in rat medullary thick ascending limb.

In vitro microperfusion experiments were performed to examine the effects of peptide hormones on bicarbonate and ammonium transport by the medullary thick ascending limb (MTAL) of the rat. Arginine vasopressin (AVP; 2.8 X 10(-10) M in the bath) reduced bicarbonate absorption by 50% (from 7.8 to 3.7 pmol/min per mm). AVP caused a similar reduction in bicarbonate absorption in tubules perfused with 10(-4) M furosemide to inhibit net NaCl absorption. Glucagon (2 X 10(-9) M in the bath) also reduced bicarbonate absorption (from 11.7 to 7.6 pmol/min per mm). The inhibition of bicarbonate absorption could be reproduced with either exogenous 8-bromo-cAMP or forskolin. With 8-bromo-cAMP (10(-3) M) in the bath, addition of vasopressin to the bath did not significantly affect bicarbonate absorption. PTH significantly inhibited bicarbonate absorption, but the extent of inhibition was less than that observed with either AVP or glucagon. Vasopressin had no effect on net ammonium absorption in MTAL perfused and bathed with 4 mM NH4Cl. These findings indicate that: (a) vasopressin, glucagon, and PTH directly inhibit bicarbonate absorption in the MTAL of the rat; (b) this inhibition occurs independent of effects on net NaCl absorption and appears to be mediated in part by cAMP; and (c) HCO3- and NH4+ absorption can be regulated independently in the MTAL.

8-Bromo Cyclic Adenosine Monophosphate↗

Growth hormone, glutamine, and a modified diet enhance nutrient absorption in patients with severe short bowel syndrome.

BACKGROUND: Massive loss of intestinal surface area results in the short bowel syndrome characterized by malabsorption of fluid, electrolytes, and other nutrients. Although the remaining bowel undergoes morphological and functional adaptation, often these changes are inadequate to support the individual by enteral feedings, and parenteral nutrition is required to prevent dehydration, electrolyte disturbances, and malnutrition. Substances such as growth hormone, glutamine, and fiber exert bowel-specific trophic effects and either directly or indirectly influence nutrient absorption. This study was undertaken to determine whether the co-administration of exogenous growth hormone, supplemental glutamine, and a modified fiber-containing diet could enhance nutrient absorption in patients who had undergone massive intestinal resection. METHODS: Ten patients (5 men, 5 women, aged 43 +/- 4 years) with short bowel syndrome were studied 6 +/- 1 years after surgical resection. All patients were admitted to the Clinical Research Center for a 28-day period; the first week served as a control period when nutritional (enteral and parenteral) and medical management simulated usual home therapy. Thereafter, eight patients received exogenous growth hormone, supplemental glutamine, and a modified high-carbohydrate, high-fiber diet. Two patients were treated with the modified diet alone. The efficiency of net nutrient absorption (percent absorbed) for total calories, protein, fat, carbohydrate, water, and sodium was calculated from the measured nutrient intake and stool losses. RESULTS: Three weeks of treatment with growth hormone, glutamine, and a modified diet increased total caloric absorption from 60.1 +/- 6.0% to 74.3 +/- 5.0% (p < or = .003), protein absorption from 48.8 +/- 4.8% to 63.0 +/- 5.4% (p < or = .006), and carbohydrate absorption from 60.0 +/- 9.8% to 81.5 +/- 5.3% (p < or = .02). Fat absorption did not change (61.0 +/- 5.3% to 60.3 +/- 7.9%, p = NS). Water and sodium absorption increased from 45.7 +/- 6.7% to 65.0 +/- 7.3% (p < or = .002) and from 49.0 +/- 9.8% to 69.6 +/- 6.5% (p < or = .04), respectively. These absorptive changes resulted in a decrease in stool output (1,783 +/- 414 g/d control period vs 1,308 +/- 404 g/d third week of treatment, p < or = .05). Treatment with diet alone did not influence nutrient absorption or stool output. CONCLUSIONS: The combined administration of growth hormone, glutamine, and a modified diet enhanced nutrient absorption from the remnant bowel after massive intestinal resection. These changes occurred in a group of patients that had previously failed to adapt to the provision of enteral nutrients. This therapy may offer an alternative to long-term dependence on total parenteral nutrition for patients with severe short bowel syndrome.

Adult↗

Concentration-dependent atypical intestinal absorption of cyclic phenylalanylserine: small intestine acts as an interface between the body and ingested compounds.

Intestinal absorption of peptides in linear form has been studied extensively, but there is little knowledge of peptides in a cyclic form. In this report, intestinal absorption of cyclic phenylalanylserine (cyclo(Phe-Ser)), a precursor of gliotoxin, was studied in isolated rat small intestine as a model cyclic dipeptide. Absorption clearance (CLabs) decreased in the presence of glycylsarcosine, cephalexin or cephradine, substrates for H+/oligopeptide cotransporter (PEPT1). CLabs of cyclo(Phe-Ser) also decreased at 4 degrees C, thus indicating that cyclo(Phe-Ser) is in part transported by PEPT1. However, the Eadie-Hofstee plot of absorption revealed an atypical profile at lower concentrations of cyclo(Phe-Ser) (around 0.1 mM). Moreover, comparative experiments of absorptive and excretive transport showed that excretive transport from the serosal to mucosal side of isolated intestinal tissue at a 0.1 mM cyclo(Phe-Ser) was superior to absorptive transport from the mucosal side to the serosal side, and vice versa at a 1 mM cyclo(Phe-Ser). A kinetic model was constructed, in which cyclo(Phe-Ser) concentration for excretive transport was assumed to be at the binding site of excretive transporter, but not the unbound cytoplasmic concentration. These results as well as the results of kinetic analysis indicate that intestinal absorption consists of passive transport, carrier-mediated absorptive transport by PEPT1 and carrier-mediated excretive transport, resulting in atypical absorption. Although cyclic dipeptides have potentials as drugs, their intestinal absorption may be complex. The results of this study lead us to conclude that absorptive and excretive transport by the small intestine acts as an interface between the body and ingested compounds.

Animals↗

Drug absorption in gastrointestinal disease and surgery. Clinical pharmacokinetic and therapeutic implications.

Drug absorption from the gastrointestinal (GI) tract and the impact of GI surgery and disease on drug absorption are discussed. Recommendations are made to manage problems of drug malabsorption. Absorption from the GI tract is a first-order process described by its rate and extent. GI surgery changes the anatomy of the GI tract and alters important variables in the absorption process. In the wake of procedures which diminish small bowel surface area, the extent of absorption of phenytoin, digoxin, cyclosporin, aciclovir, hydrochlorothiazide and certain oral contraceptives is reported to be reduced. The underlying cause of the reduction is unknown. When gastric emptying time or pH are altered by surgery, the rate of drug absorption appears to be reduced. However, it is not clear which variable is more important in determining therapeutic effects. The effects of coeliac and inflammatory bowel diseases on the distribution and clearance of drugs must be considered before attributing abnormal serum concentrations of drugs to malabsorption. GI disease may slow gastric emptying and delay the complete absorption of drugs when their rate of absorption depends on gastric emptying time. Other inflammatory GI diseases such as graft-versus-host disease (GVHD) of the gut, Behçet's syndrome and scleroderma involving the GI tract may directly reduce absorption of drugs such as cyclosporin, amitriptyline, benzodiazepines, anticonvulsants, paracetamol (acetaminophen) and penicillamine. GI diseases which alter gut pH affect the absorption only of drugs with limited water solubility and pH-dependent dissolution such as ketoconazole. Clinicians should be aware of the variable absorption seen after GI disease and surgery and monitor their patients accordingly.

Gastrointestinal Diseases↗

Absorption of magnesium and other macrominerals in sheep infused with potassium in different parts of the digestive tract.

Two metabolism trials were conducted with 12 crossbred wether lambs, each surgically equipped with a ruminal catheter and abomasal and ileal cannulae, to study the effect of K infusion in different sites of the digestive tract on site of absorption and flow of minerals. The treatments consisted of the infusion of 33.6, 12.0 or 12.0 g K/d as bicarbonate into either the rumen, abomasum or ileum, respectively. Each trial consisted of a minimum 5-d preliminary period, five 3-d collection periods to determine mineral balance and a 6-d sampling period to determine mineral flow and site of absorption. Chromic oxide was incorporated into the diet for use as a marker. Magnesium was absorbed primarily from the preintestinal region. Ruminal infusion of K tended to decrease preintestinal Mg absorption. Absorption of Mg in the entire tract was decreased (P less than .05) 43% when K was infused into the rumen. There was a slight absorption of Mg in the small intestine, followed by a net secretion into the large intestine. Serum Mg levels tended to be depressed in lambs infused with K intraruminally. Calcium flow from the preintestinal region was decreased (P less than .05) by infusion of K into the rumen. Only lambs infused with K in the rumen had a net secretion of Na into the small intestine. The large intestine was the primary site of net Na absorption for ruminal-infused lambs. Phosphorus flow from the preintestinal region was decreased (P less than .05) by infusion of K into the rumen. Potassium flow from both the preintestine and small intestine was increased (P less than .05) by ruminal K infusion. The infusion of K into the rumen, abomasum or ileum increased (P less than .05) the total absorption of K, with the small intestine being the major absorptive site. The infusion of potassium bicarbonate into the rumen of sheep raised (P less than .05) the pH of the ruminal contents 15%. Ruminal infusion of K depresses Mg absorption, while the infusion of K into the abomasum or ileum does not affect Mg absorption. Therefore, the role of K in grass tetany may be via this depression of Mg absorption.

Abomasum↗

A new aspect on the mechanism of intestinal cholesterol absorption in rat.

In order to study the mechanism of intestinal cholesterol absorption, the relationship between the amount of cholesterol administered and the rate of absorption was investigated by the dual isotope plasma ratio method in vivo and the ligated-loop method in situ. The energy requirement of cholesterol absorption was also observed by means of the ligated-loop method. The results obtained are summarized below. 1) Tri-phase absorption was observed by the dual isotope plasma ratio method. When less than 300 microgram of cholesterol was administered, absorption increased linearly, with the coefficient of absorption being more than 80%. When the amount administered was between 300 and 500 microgram, the absorption was constant. With the administration of more than 500 microgram, absorption increased linearly, but the coefficient of absorption decreased to approximately 55%. 2) With the ligated-loop method, a second saturation profile was obtained when between 250 and 400 microgram of cholesterol was administered to a segment. When 50 to 250 microgram of cholesterol were administered, absorption increased in proportion to the increase in cholesterol dosage. 3) The mucosal uptake of cholesterol decreased to 40-60% of the control with the addition of metabolic inhibitors such as NaN3, KCN, 2,4-DNP and ouabain, whereas the uptake of palmitate showed no significant decrease. In addition, the uptake of cholesterol decreased remarkably to 25% of the control with the lowering of body temperature from 37 degrees C to 27 C. These results suggest the existence of an active transport system which has a limited capacity for cholesterol absorption and which requires energy for its operation in the physiological state.

Animals↗

Influence of dietary electrolytes on lysine and arginine absorption in chick intestine.

The intestinal absorption of lysine and arginine in the chick was characterized using an in situ-ligated intestinal segment technique, and the influence of dietary electrolytes on their absorption was examined. Each amino acid, labeled with 14C and provided at a concentration of .5 mM, was introduced into the lumen of the small intestine of young chicks. Absorption was defined as disappearance of label from the lumen after 4 min. Lysine absorption was greater than arginine absorption in the duodenum and in the middle and distal small intestine. The Jmax values for absorption of lysine and arginine were 315.0 nmol/min and 112.0 nmol/min, whereas the respective Kt values were 2.3 mM and 2.0 mM. Maximal transport of lysine and arginine occurred at pH 6.0. Lysine absorption was depressed (P less than .05) at pH 5.0 and pH 8.0, whereas arginine absorption was depressed (P less than .05) only at pH 8.0. High dietary chloride (.89%) produced higher (P less than .05) lysine absorption than a high dietary level of potassium (1.81%). No effect (P greater than .05) of dietary electrolytes on arginine absorption was detected. These results indicate that the dietary balance of monovalent electrolytes, and, hence, acid-base balance, may influence the intestinal absorption of lysine.

Analysis of Variance↗

Effect of perfusion rate on absorption, surface area, unstirred water layer thickness, permeability, and intraluminal pressure in the rat ileum in vivo.

Intestinal absorption and intraluminal pressures were measured at perfusion rates between 0.3 and 200 ml per min in the rat ileum in vivo. Glucose absorption from a 72 mM glucose solution and tritiated water ([3-H]water) diffusion rate were used to reflect changes in mucosal surface area. Glucose absorption from a 4 mM solution was used to indicate changes in unstirred water layer thickness, and mannitol and urea absorption were used as markers of passive mucosal permeability. In a partially obstructed intestinal segment, designed to keep the gut partially filled even at low perfusion rates and to minimize surface area change as perfusion rate was increased, glucose absorption from a 4 mM solution increased by 150% as perfusion rate was increased from 1 to 100 ml per min. Forty per cent of this increase was due to increased surface area (estimated from the change in [3-H]water absorption), and 110% of the increase is attributed to thinning of the unstirred water layer. Because mannitol absorption was zero at all perfusion rates, none of the enhanced glucose absorption rate need be attributed to enhanced mucosal permeability, even though intraluminal pressure was increased at higher perfusion rates. Urea absorption was apparently influenced by surface area and by permeability changes, but not by the thickness of the unstirred water layer. This model was also used to explore the effect of unstirred water layer thickness on the inhibitory effect of sodium replacement by magnesium on glucose absorption from a 4 mM glucose solution. Inhibition by sodium removal was equal at 1, 10, 100, and 200 ml per min perfusion rates, suggesting that unstirred water layer thickness does not play an important role in the interaction of glucose and sodium absorption when intraluminal sodium concentration is reduced. Additional experiments in an unobstructed ileal segment revealed that the major effect of enhanced perfusion rate is to increase mucosal surface area; relatively high rates of perfusion were required to thin significantly the unstirred water layer when intestinal outflow was not partially obstructed.

Animals↗

Effect of bile salts, lipid, and humic acids on absorption of benzo[a]pyrene by isolated channel catfish (Ictalurus punctatus) intestine segments.

Dietary absorption of lipophilic contaminants may be a significant route of exposure in aquatic organisms. Bile salts, lipids, and humic acids are important factors that may influence the intestinal absorption of a contaminant such as benzo[a]pyrene (BaP). We hypothesized that bile salts, monoglycerides, and free fatty acids would increase BaP intestinal absorption, while triglycerides, humic acids, and sediment would decrease BaP intestinal absorption. We have established and validated an in vitro model to examine modification of 3H-BaP absorption in everted intestinal segments from channel catfish (Ictalurus punctatus). Uptake of BaP into the everted intestinal segments continued to increase over the times examined in this study (60 min) and apparently occurs passively; thus, fugacity-based models of uptake are supported. Absorption of BaP into intestinal cells was significantly decreased by the addition of monoglycerides and free fatty acids to bile salts in the incubation media. Addition of triglycerides decreased BaP absorption even further. Humic acids may have decreased BaP intestinal absorption, while natural sediment may have increased BaP absorption. The results of this study suggest that all lipids may decrease intestinal uptake of lipophilic contaminants if they remain in unabsorbable excess in the intestinal lumen by retaining BaP in lipid/bile micelles. In contrast, if triglycerides are hydrolyzed into monoglycerides/free fatty acids prior to absorption, lipophilic contaminant uptake will likely be facilitated. Thus, it may be the hydrolytic state of lipids that determines its effects on BaP absorption. Humic acids alone may decrease dietary uptake of BaP, but our results suggest that other components in natural sediment may counteract this effect to cause a slight enhancement of BaP uptake. Further studies are needed to determine the dietary conditions necessary for bioaccumulation to contribute significantly to lipophilic contaminant body burdens in benthivorous fish. Finally, the everted intestinal segment technique has the potential to be used in other species and with different contaminants.

Animals↗

Nutrition and magnesium absorption: a review.

This paper reviews the evidence that certain dietary components can affect intestinal absorption of magnesium. Increased intakes of protein and fructose improve apparent magnesium absorption (magnesium intake minus fecal excretion) in humans, whereas a lowering effect occurs with consumption of cellulose and phytate. Although dietary concentrations of lactose, fat, calcium and phosphate have clear effects on magnesium absorption in experiments with rats, the impact of these nutrients on magnesium absorption in humans remains unsettled. Mechanisms underlying the effects of dietary components on magnesium absorption in humans are generally poorly understood. A change in magnesium absorption not necessarily results in a change in magnesium retention. When consuming practical diets, the fall of apparent magnesium absorption caused by phytate and cellulose is generally compensated by increased magnesium intake due to high magnesium concentrations in phytate- and cellulose-rich products. Furthermore, to maintain homeostasis, urinary magnesium excretion will be raised after stimulation of apparent magnesium absorption and it will be lowered after impairment of apparent magnesium absorption. Thus, the effects of dietary components on magnesium absorption probably are critically important only at low intakes of magnesium. At low magnesium intakes, differences in magnesium absorption may be expected to influence magnesium retention and thus can either induce or abolish magnesium deficiency.

Animals↗

[Chromophoric dissolved organic matter absorption characteristics with relation to fluorescence in typical macrophyte, algae lake zones of Lake Taihu].

Chromophoric dissolved organic matter (CDOM) represents one of the primary light-absorbing species in natural waters and plays a critical in determining the aquatic light field. CDOM shows a featureless absorption spectrum that increases exponentially with decreasing wavelength, which limits the penetration of biologically damaging UV-B radiation (wavelength from 280 to 320 nm) in the water column, thus shielding aquatic organisms. CDOM absorption measurements and their relationship with dissolved organic carbon (DOC), and fluorescence are presented in typical macrophyte and algae lake zone of Lake Taihu based on a field investigation in April in 2004 and lab analysis. Absorption spectral of CDOM was measured from 240 to 800 nm using a Shimadzu UV-2401PC UV-Vis recording spectrophotometer. Fluorescence with an excitation wavelength of 355 nm, an emission wavelength of 450 nm is measured using a Shimadzu 5301 spectrofluorometer. Concentrations of DOC ranged from 6.3 to 17.2 mg/L with an average of 9.08 +/- 2.66 mg/L. CDOM absorption coefficients at 280 nm and 355 nm were in the range of 11.2 - 32.6 m(-1) (average 17.46m(-1) +/- 5.75 m(-1) and 2.4 - 8.3 m(-1) (average 4.17m(-1) +/- 1.47 m(-l)), respectively. The values of the DOC-specific absorption coefficient at 355 nm ranged from 0.31 to 0.64 L x (mg x m)-1. Fluorescence emission at 450 nm, excited at 355 nm, had a mean value of 1.32nm(-1) +/- 0.84 nm(-1). A significant lake zone difference is found in DOC concentration, CDOM absorption coefficient and fluorescence, but not in DOC-specific absorption coefficient and spectral slope coefficient. This regional distribution pattern is in agreement with the location of sources of yellow substance: highest concentrations close to river mouth under the influence of river inflow, lower values in East Lake Taihu. The values of algae lake zone are obvious larger than those of macrophyte lake zone. In Meiliang Bay, CDOM absorption, DOC concentration and fluorescence tend to decreasing from inside to mouth of the Bay. The results show a good correlation between CDOM absorption and DOC coefficients during 280 - 500 nm short wavelength intervals. The R-square coefficient between CDOM absorption and DOC concentration decreases with the increase of wavelength from 280 to 500 nm. The significant linear regression correlations between fluorescence, DOC concentration and absorption coefficients were found at 355 nm. The exponential slope coefficients ranged from 13.0 to 16.4 microm(-1) with a mean value 14.37microm(-1) +/- 0.73microm(-1), 17.3microm(-1) - 20.3microm(-1) with a mean value 19.17microm(-1) +/- 0.84microm(-1) and 12.0microm(-1) - 15.8microm(-1) with a mean value 13.38microm(-1) +/- 0.82microm(-1) over the 280 - 500 nm, 280 - 360 nm and 360 - 440 nm intervals.

Absorption↗

[Absorption of enzymatic protein hydrolysates and equimolar amino acid mixtures in the perfused small intestine of the rat].

Casein, wheat gluten or field-bean protein isolate (vicia faba) was hydrolyzed enzymatically by trypsin or thermitase (proteinase from Thermoactinomyces vulgaris). The degree of splitting of the protein peptide bounds was, resp., 18% or 30% for casein, 8% or 30% for wheat gluten and 16% or 29% for the field-bean protein isolate. The peptide pattern of the protein hydrolysates was measured by gel chromatography. The absorption of the enzymatic protein hydrolysates was compared with the absorption of the equimolar mixtures of free amino acids by perfusion of the distal or proximal part of the small intestine of nonanaesthesized rats. The absorption was measured on the basis of the amino acid disappearance from the perfused part of the small intestine and expressed as absorption of the total amino acids, of each single amino acid and as coefficient of variation of amino acid absorption. There are no differences in the total amino acid absorption of the tryptic casein hydrolysate and the three thermitatic protein hydrolysates compared with their corresponding mixtures of free amino acids. The absorption is decreased in case of larger oligopeptides. Their preceding mucosal hydrolysis is slower than the absorption of the splitting products. This is true for tryptic hydrolysates of wheat gluten and field-bean protein. The absorption patterns of the single amino acids are different for protein hydrolysates compared with their equimolar mixtures of amino acids in case of a same total absorption, too. The coefficient of variation is low (more equal amino acid absorption) in hydrolysates consisting of a homogeneous mixture of low molecular weight peptides. It is more increased in mixtures of free amino acids or in hydrolysates containing longer-chain peptides.

Animals↗

Influence of glucose, fructose, and water movement on calcium absorption in the jejunum.

The first experiment demonstrated that glucose stimulated calcium absorption. Possible mechanisms include: (a) glucose stimulation of active calcium absorption, (b) glucose stimulation of water absorption with enhanced calcium absorption by solvent drag, or (c) glucose stimulation of water absorption caused an increased luminal calcium concentration with resultant increased active and/or passive calcium absorption. In a second experiment, neither glucose, fructose of water absorption stimulated calcium absorption when luminal calcium concentration was maintained at a constant level. These results suggest: (a) glucose and fructose indirectly enhance calcium absorption via an effect on water movement, (b) water absorption enhances calcium absorption by virtue of concentrating unabsorbed calcium within the intestinal lumen, not by solvent drag, and (c) bulk water movement and passive calcium ion movement take place via separate channels.

Biological Transport↗

Na+/H+ exchange mediates meal-stimulated ileal absorption.

BACKGROUND: The ingestion of a meal increases water and electrolyte absorption from the jejunoileum. Recent observations have implicated Na(+)-glucose cotransport as a primary mediator of meal-stimulated jejunal absorption. The current experiments tested the hypothesis that Na+/H+ exchange is a major mediator of basal and meal-stimulated ileal absorption. METHODS: Absorption studies (n = 36) were performed on dogs with 25 cm ileal Thiry-Vella fistulas. Six groups were studied for 4 hours. Luminal perfusion with 14C-polyethylene glycol was used to calculate absorption of water, sodium, chloride, and glucose. A 480 kcal canine meal was ingested in groups 2, 3, 5, and 6. Luminal amiloride (1 mmol/L) was used to inhibit Na+/H+ exchange in groups 1, 3, 4, and 6. To assess Na(+)-glucose cotransport the luminal perfusate contained either 10 mmol/L glucose (groups 1 through 3) or 10 mmol/L mannitol, a nontransported hexose (groups 4 through 6). RESULTS: Ileal absorption increased significantly in response to a meal in the presence of both glucose (group 2) and mannitol (group 5). Amiloride caused a significant reduction in basal and postmeal water and electrolyte absorption, largely independent of the glucose-mannitol content of the luminal perfusate. Mannitol significantly reduced basal absorption of water and electrolytes. CONCLUSIONS: These data indicate that both Na+/H+ exchange and Na(+)-glucose cotransport contribute to basal ileal water and electrolyte absorption, whereas Na+/H+ exchange appears to be the primary mediator of meal-stimulated ileal absorption. Na+/H+ exchange appears to play a major role in the physiologic regulation of postprandial ileal absorption.

Amiloride↗

Intestinal absorption during rest and exercise: implications for formulating an oral rehydration solution (ORS). Proceedings of a roundtable discussion. April 21-22, 1993.

Formulation of oral rehydration solutions (ORS) is reviewed in the context of methods for measuring absorption of water and component substrates, transport mechanisms of substrates and water, requirements of the athlete, and effects of exercise on absorption. The triple lumen tube intubation perfusion method is the optimal technique for obtaining absorption data from the human small intestine during rest and exercise. Factors that must be considered when interpreting absorption data obtained by this technique include the role of the mixing segment in altering composition of the infused solution, defining optimal segment length, effects of ORS osmolality, and absorption of "nonabsorbed" indicators. Absorption data are applicable only to the test segment and may lack relevance to ORS transport proximal and distal to the test segment. Absorption rate of an ORS measured by perfusion may not correlate with absorption rate following ingestion. Transport of water, electrolytes, carbohydrates, and other solutes including glutamine and amino acids is considered in relation to ORS formulation. Factors affecting absorption of an ORS including the unstirred layer, motility, intestinal blood flow, and maximal absorptive capacity of the alimentary tract are considered. Exercise per se at 30-70% VO2max for 60-90 min probably has minimal effects in limiting absorption of an ORS. Consideration relevant to supplying needs of the athlete during prolonged exercise in relation for ORS formulation are discussed.

Animals↗