Ca2(+)-dependent glucose transport in chicken intestine

Transport of glucose was measured in the intestine of white leghorn layers in vivo using ligated upper small intestinal segment in the presence of Ca2+ and other ions either singly or in combination. Transport of glucose across the intestine was very significantly increased with Ca2+ than Na+, K+ and Po4(3-) individually, but when Ca2+ was combined with Na+, K+ and PO4(3-), the glucose absorption increased significantly over that achieved by Na+ ions alone. These data revealed that Ca2+ ions might be exerting the major influence on glucose transport processes of the chicken intestine.     

Effect of hypophysectomy on absorption of inorganic phosphate by the eel intestine

Hypophysectomy of freshwater-adapted eels resulted in a marked reduction in net absorption of PO4(3-) in the non-stripped and non-everted intestine. Stanniectomy was without effect on net movements of water and electrolytes in this isolated eel preparation. Repeated injections of eel calcitonin into the eel, kept either in deionized water or 10 mM CaCl2, had no effect on net absorption of water and electrolytes, including Ca2+ and PO4(3-). In the stripped and everted intestine, the net PO4(3-) absorption was significantly greater in the fed eel than in the starved fish. Hypophysectomy of the fed eel resulted in a significant reduction, not only in PO4(3-) absorption, but also in absorption of water and other electrolytes. It is suggested that pituitary hormone is involved in the intestinal PO4(3-) absorption of the eel.     

The effect of aging on intestinal absorption and status of calcium, magnesium, zinc, and copper in rats: A stable isotope study

Many investigators have reported changes in mineral status with age but conflicting observations were done concerning mineral absorption. This study was conducted to clarify the effect of aging on intestinal absorption and status of minerals, using a stable isotope approach. To do so, 40 rats of different ages: 9, 22, 44, and 88 weeks were fed with a semi-purified diet for a total of 30 days. At the beginning of the 4th week, the rats received a stable isotope solution containing (44)Ca, (25)Mg, (67)Zn, and (65)Cu. Individual feces and urine were then collected during 4 consecutive days in order to measure stable isotopes by inductively coupled plasma/mass spectrometry (ICP/MS) and blood and tissues were sampled for mineral status determination. Intestinal absorption of (44)Ca and (67)Zn considerably decreased with age, whereas intestinal (25)Mg absorption decreased only moderately and intestinal (65)Cu absorption was unaffected. Plasma and bone calcium (Ca) were not modified with age whereas urinary Ca excretion considerably increased. Plasma and erythrocyte magnesium (Mg) levels were unaffected with age whereas urinary Mg excretion and Mg bone level decreased. Plasma zinc (Zn) level decreased and bone Zn level increased with age whereas red blood cell and liver Zn level and urinary Zn excretion remained unchanged. Plasma Cu level increased with age whereas liver and bone Cu levels and urinary Cu excretion remained unchanged. These results show that the effect of aging on the intestinal mineral absorption and status differ largely according to the mineral considered. Further studies are required under different nutritional conditions to explore the underlying mechanisms during aging and to adjust a better nutrition of the elderly.     

The effect of the anions, phosphate and sulphate, on normal rates of excretion of potassium in dogs.

Small doses of (NH4)2HPO4 or KH2PO4 by stomach tube caused increase in plasma PO4 and PO4 excretion. Above a threshold of 0-8 mmol. 1(-1), increase of plasma PO4 by 0-5 mmol. 1(-1) caused PO4 excretion to increase by about 35 mumol. min.-1 After KH2PO4 this relationship was not altered by the concurrent increases in plasma K and K excretion. After doses of (NH4)2SO4 or K2SO4, excretion of SO4 was similarly related to plasma SO4 and was independent of plasma K and K excretion. An effect of PO4 on K excretion was observed after doses of (NH4)2HPO4, when increased excretion of PO4 was accompanied by increased excretion of K without change in plasma K. There was also increased excretion of NH4 and a small increase in Na excretion. The changes were similar to those produced by (NH4)2SO4 [O'Connor and Summerill, 1976]. KH2PO4 and K2SO4 produced increase in plasma K and increased excretion of K not significantly different from the changes produced by KCl or KHCO3 [Baylis and O'Connor, 1976]. After KH2PO2 or K2SO4, the urinary anion was PO4 or SO4, instead of Cl and HCO3. Any effect of anions on K excretion was much less than the effect of increase in plasma K. At low rates of excretion of K, increased urinary excretion of impermeant anion can determine increased excretion of K. However, the effect of anion is small in comparison with the effect of increase in plasma K.     

Control of ion and fluid transport by putative second messengers in different segments of the Malpighian tubules of the black field cricket Teleogryllus oceanicus

The differences in second messenger control of secretion were investigated in the distal and main segments of the Malpighian tubules of the black field cricket Teleogryllus oceanicus. Secretion by the main segment was considerably increased by corpora cardiaca extract and db-cAMP. Corpora cardiaca had no effect on secreted fluid composition or intracellular elemental composition but db-cAMP increased Na(+) and Cl(-) transport, as measured by x-ray microanalysis of secreted fluids and cells. Secretion by the main segment was considerably increased by forskolin and by Sp-cAMP. Secretion in the distal segment was abolished by corpora cardiaca extract but was unaffected by db-cAMP and only slightly reduced by 8-bromo-cAMP. However, Sp-cAMP increased secretion but forskolin reduced secretion. The responses of the distal segment suggest the possibility of a multiplicity of controls through different protein kinases and adenylyl cyclases. Secretion rate in the main segment was also increased by cGMP but distal segment secretion was unaffected. Secretion from both segments was increased by 5-HT. In the main segment secretion rate was increased by Ca-ionophore and thapsigargin and decreased by verapamil. This suggests a role for Ca(2+) as a controlling second messenger. In the distal segment only Ca-ionophore had an effect on secretion rate, which was reduced. Secretion rates in both segments were decreased in Ca-free saline. In saline in which Sr(2+) replaced Ca(2+), secretion rate in the main segment was greatly increased whilst that of the distal segment was decreased, suggesting that Sr(2+) could substitute for Ca(2+) as a second messenger.     

The effect of calcium on lead absorption in rats.

The effects of Ca2+ on lead absorption as PbCl2 and 203PbCl2 were studied in rats. 1. Doubling of dietary calcium with Ca3(PO4)2 significantly decreased lead absorption as assessed by 203Pb retention, tissue lead concentration, urinary excretion of delta-aminolaevulinate and increased activities of delta-aminolaevulinate dehydratase and ferrochelatase. 2. Similar effects on lead absorption were shown by the Ca2+ salts, Cl-, CO32-, PO43-, SO42-, gluconate and glycerophosphate. 3. CaCl2 and calcium glycerophosphate were found to be most effective in decreasing lead absorption when administered immediately before lead dosage. 4. A negative exponential relationship was found between CaCl2 concentration and 203Pb absorption at 120h. The result suggest that, above 4 mmol of administered calcium, residual lead absorption is unaffected by increasing gastrointestinal calcium concentrations. 5. Increased systemic calcium had no effect on lead retention. 6. Calcium in the concentrations found in domestic hard-water supplies significantly decreased absorption of a solution of 203Pb dissolved in it compared with absorption of 203Pb dissolved in soft or distilled water. 7. Milk and skimmed milk were found to have no effect on 203Pb absorption in rats.     

微型生态系统中浮游动物正磷酸盐排泄率的估算

在考查罗非鱼或鲢、鳙下行影响的微型生态系统实验后期,对其唯一的浮游动物──大型的特定正磷酸盐(PO4-P)排泄率按不同大小级别和培育时间进行了测定,同时估算了该浮游动物种群的PO4-P排泄率。结果表明,大型的特定PO4-P排泄率依其体重的增长呈指数式下降,并且随着培育时间的增加而大大降低。有鱼系统中大型种群的PO4-P排泄率及其与浮游植物PO4-P摄取率的比值都显著地小于无鱼系统,而放养罗非鱼或鳙的系统之二项估算值又明显地比鲢单养系统低。看来,大型种群的磷排泄在鲢单养系统的PO4-P再生中起有一定的作用,而在放养罗非鱼或鳙的系统中所起的作用很小。       

Ethanol and the antioxidant defense in the gastrointestinal tract.

Ethanol is known to have profound actions on the gastrointestinal tract. The present study was undertaken to examine the effects of ethanol on some of the natural antioxidant defensive enzymes in the gastrointestinal tract; the activities of these enzymes in the liver and the brain were also measured for comparison with those in the gastrointestinal tract. Oral administration of absolute ethanol induced severe gastric mucosal lesions and also damage in the small intestine, however the total superoxide dismutase was unaffected in the tissues measured. The glucose-6-phosphate dehydrogenase activity was reduced only in the stomach while the total glutathione was elevated in the small intestinal mucosa. The catalase activities were activated in the stomach, small and large intestines, and brain, but not in the liver which contained the highest concentration of the enzyme. The present findings indicate that endogenous hydrogen peroxide may be an important damaging agent towards biomolecules in different organs and the removal of this by catalase represents an important defensive mechanism against ethanol toxicity.     

Contribution of diet to the dosing time-dependent change of vitamin D3-induced hypercalcemia in rats

We have recently reported that the degree of hypercalcemia as an adverse effect induced by a single large-dose of active vitamin D3 varied with its dosing time without alteration in therapeutic effect for secondary hyperparathyroidism in patients with chronic renal failure. The present study was conducted to elucidate an effect of intestinal calcium (Ca) absorption on the chronopharmacological profiles of vitamin D3. 1, 25-dihydroxy-cholecalciferol (D3, 2 microg/kg) or vehicle alone was orally administered at two different times (2 and 14 hours after lights on; HALO) to male Wistar rats (n= 10) kept in rooms with a 12 h light-dark cycle. Blood samples for serum Ca concentration were taken before and 3, 6, 9, and 12 hours after the administration. Urine was collected for 6 hours after dosing. An identical protocol was repeated using the same animals after 16 hours fasting by a cross-over fashion. Under free-fed condition, basal concentration of serum Ca was higher at a resting period (lights on) than during an active period (lights off). Serum Ca reached its peak at 6 hours after dosing in both timings, while the value was significantly higher in the 2 HALO trial than in the 14 HALO trial. Area under the serum Ca concentration-time curve from 0 to 12 hours (AUC0-12h) and urinary excretion of Ca for 6 hours were also significantly higher in the 2 HALO trial than in the 14 HALO trial. When fasted, basal Ca concentration was reduced compared with the free-fed condition, while the daily variation was maintained. Serum Ca concentration profiles from 3 to 12 hours after dosing were not significantly different between the 2 HALO and 14 HALO trials. The AUC0-12h of serum Ca or its urinary excretion was not different between both trials. Serum concentrations of parathyroid hormone and total protein, measured before and 6 hours after the dosing were not affected by the dosing schedule. We have concluded that intestinal Ca absorption is a major factor for the chronopharmacological phenomenon of D3-induced hypercalcemia in intact rats, while intestinal and renal involvement may be relatively small in the mechanism of the intrinsic diurnal variation of serum Ca.     

Effects of dietary zinc depletion and food restriction on intestinal transport of cadmium in the rat

The effects of Zn depletion and short-term fasting on intestinal transport of Cd were examined in perfused rat small intestines. The small intestine was isolated with its vascular network intact, then simultaneously perfused from the luminal and vascular sides. A Zn-depleted state that results in marked hypozincemia was produced in some rats by feeding a Zn-deficient diet for 4 days. Uptake of Cd from the luminal perfusate was greater in the Zn-depleted rats, whereas transport of Cd to the vascular perfusate was not affected. Fasting overnight prior to perfusion did not influence Cd transport nor alter the effect of Zn depletion on Cd uptake. The Cd concentration in the soluble fraction of intestinal mucosa from perfused intestines was not different between Zn-depleted and Zn-adequate rats. Gel filtration chromatography of the soluble fraction showed a shift in the distribution of Cd from metallothionein to high molecular weight ligands in intestines from Zn-depleted rats. The decrease in amount of metallothionein-associated Cd corresponded to a decrease of total intestinal metallothionein as measured by the Cd-binding assay. The results suggest association of Cd with intestinal metallothionein did not influence the absorption of Cd under these conditions.     

Lack of the intestinal Muc1 mucin impairs cholesterol uptake and absorption but not fatty acid uptake in Muc1-/- mice

Before cholesterol and fatty acid molecules in the small intestinal lumen can interact with their possible transporters for uptake and absorption, they must pass through a diffusion barrier, which may modify the kinetics of nutrient assimilation. This barrier includes an unstirred water layer and a surface mucous coat, which is located at the intestinal lumen-membrane interface. In the present study, we investigated whether disruption of the mucin gene (Muc)1 may influence intestinal uptake and absorption of cholesterol and fatty acid in male Muc1(-/-) mice. The wild-type mice displayed relatively high levels of Muc1, Muc2, Muc3, and Muc4 mRNAs and relatively low levels of Muc5ac and Muc5b mRNAs in the small intestine. The absence of Muc1 mRNA and protein in the small intestines of Muc1(-/-) mice confirmed complete knockout of the Muc1 gene, but the mRNA expression for other mucin genes remained unchanged. Intestinal uptake and absorption of cholesterol but not palmitic acid were significantly reduced in Muc1(-/-) mice compared with the wild-type mice. However, knockout of the Muc1 gene did not impair either expression levels of the genes that encode intestinal sterol efflux transporters Abcg5 and Abcg8 and fatty acid transporter Fatp4 or small intestinal transit rates. We conclude that physiological levels of the epithelial mucin produced by the Muc1 gene are necessary for normal intestinal uptake and absorption of cholesterol in mice. Our study implies that because cholesterol absorption efficiency is reduced by approximately 50% in Muc1-deficient mice, there may be one or more additional pathways for cholesterol absorption.     

Electroneutral cation-Cl- cotransporters NKCC2β and NCCβ expressed in the intestinal tract of Japanese eel Anguilla japonica

In the present study, we aimed to elucidate the mechanisms of intestinal Na(+) and Cl(-) absorption in Japanese eel, focusing on electroneutral cation-Cl(-) cotransporters, NKCC2β and NCCβ, expressed in the intestinal tract. First, we cloned cDNAs encoding NKCC2β and NCCβ from the intestinal tract of Japanese eel. In both freshwater- and seawater-acclimated eels, quantitative PCR analysis showed that NKCC2β was predominantly expressed in the anterior and posterior intestines, and that NCCβ expression was specifically high in the rectum. According to immunohistochemistry with anti-eel NKCC2β (reacting with NKCC2β but not with NCCβ) and T4 antibody (reacting with both NKCC2β and NCCβ), NKCC2β was localized in the apical surface of the epithelial cells in the anterior and posterior intestines, whereas NCCβ was likely to be distributed to that in the rectum. Furthermore, a specific NCC inhibitor, hydrochlorothiazide, inhibited of Na(+) and Cl(-) absorption, as well as water absorption, in the rectal sac preparations from seawater eel, indicating the involvement of NCCβ in ion absorption in the rectum. Our findings indicate that NKCC2β expressed in the anterior and posterior intestines and NCCβ in the rectum are importantly involved in ion absorption to reduce osmolality of ingested seawater prior to water absorption in seawater-acclimated eel.     

Mechanism for the cholesterol-lowering action of egg white protein in rats

Eggs are a popular source of dietary cholesterol, but their consumption does not necessarily result in an increased serum cholesterol concentration. We investigated the cholesterol-lowering activity of egg white protein (EWP) and its potential mechanism in rats. The consumption of EWP resulted in a decreased concentration of cholesterol in the serum, liver and intestinal mucosa. The excretion of fecal neutral sterols and bile acids was greater by rats fed with EWP than by those fed with casein. The ratio of cholesterol and bile acids in the micellar phase to those in the solid phase was lower in the intestinal contents from rats fed with EWP than from those fed with casein. These results suggest that the cholesterol-lowering activity of EWP can be attributed to lowering the cholesterol absorption by intervening in the micellar formation in the intestines.     

Iron absorption by Belgrade rat pups during lactation

Divalent metal transporter-1 (DMT1) mediates dietary nonheme iron absorption. Belgrade (b) rats have defective iron metabolism due to a mutation in the DMT1 gene. To examine the role of DMT1 in neonatal iron assimilation, b/b and b/+ pups were cross-fostered to F344 Fischer dams injected with (59)FeCl(3) twice weekly during lactation. Tissue distribution of the radioisotope in the pups was determined at weaning (day 21). The b/b pups had blood (59)Fe levels significantly lower than b/+ controls but significantly higher (59)Fe tissue levels in heart, bone marrow, skeletal muscle, kidney, liver, spleen, stomach, and intestines. To study the pharmacokinetics of nonheme iron absorption at the time of weaning, (59)FeCl(3) was administered to 21-day-old b/b and b/+ rats by intragastric gavage. Blood (59)Fe levels measured 5 min to 4 h postgavage were significantly lower in b/b rats, consistent with impaired DMT1 function in intestinal iron absorption. Tissue (59)Fe levels were also lower in b/b rats postgavage. Combined, these data suggest that DMT1 function is not essential for iron assimilation from milk during early development in the rat.     

Effects of vitamin D receptor inactivation on the expression of calbindins and calcium metabolism

Hypocalcemia, rickets, and osteomalacia are major phenotypic abnormalities in vitamin D receptor (VDR)-null mice. In an attempt to understand the abnormal regulation of calcium metabolism in these animals, we examined the expression of calbindins (CaBP) as well as calcium handling in the intestine and kidney of VDR null mice. In adult VDR-null mice, intestinal and renal CaBP-D9k expression was reduced by 50 and 90%, respectively, at both the mRNA and protein levels compared with wild-type littermates, whereas renal CaBP-D28k expression was not significantly changed. Intestinal calcium absorption was measured by the rate of (45)Ca disappearance from the intestine after an oral dose of the isotope. (45)Ca absorption was similar in VDR-null and wild-type mice, but the amount of (45)Ca accumulated in the serum and bone was 3-4 times higher in wild-type mice than in VDR-null mice. Despite the hypocalcemia, the urinary excretion of calcium in VDR-null mice was not different from that in wild-type mice. Moreover, 1 wk of a high-calcium diet treatment that normalized the serum ionized calcium level of VDR-null mice increased the urinary calcium level of these mutant mice to twofold higher than that of wild-type mice on the same diet, suggesting impaired renal calcium conservation in VDR-null mice. These data demonstrate that renal CaBP-D9k, but not CaBP-D28k, is highly regulated by the VDR-mediated action of 1,25-dihydroxyvitamin D(3). Furthermore, the results also suggest that impaired calcium conservation in the kidney may be the most important factor contributing to the development of hypocalcemia in VDR-null mice, and CaBP-D9k may be an important mediator of calcium reabsorption in the kidney.     

Intestinal bicarbonate secretion in marine teleost fish-source of bicarbonate, pH sensitivity, and consequences for whole animal acid-base and calcium homeostasis

Whole animal studies using seawater European flounder (Platichthys flesus) revealed that increasing intestinal [Ca(2+)] to 20 mM stimulated net HCO(3)(-) base secretion by 57%, but this was effectively balanced by an increase in net acid secretion, likely from the gills, to maintain whole animal acid-base status. Higher Ca(2+) concentrations (40 and 70 mM) in ambient seawater resulted in reduced plasma total CO(2). This indicates (1) imperfect acid-base compensation, and (2) that endogenous metabolic CO(2) is insufficient to fuel intestinal HCO(3)(-) secretion, under hyper-stimulated conditions. Bicarbonate secretion plays an important role in preventing calcium absorption by precipitating a large fraction of the imbibed calcium as CaCO(3). Indeed, under high Ca(2+) conditions (20 mM), up to 75% of the intestinal Ca(2+) is precipitated as CaCO(3) and then excreted. This is undoubtedly important in protecting the marine teleost kidney from the need for excessive calcium excretion and risk of renal stone formation. Using an in vitro pH-stat technique with the isolated intestinal epithelium, the replacement of serosal CO(2) with a HEPES buffered saline had no effect on HCO(3)(-) secretion, indicating that the endogenous supply of HCO(3)(-) from CO(2) hydration within epithelial cells is adequate for driving baseline secretion rates. Further, in vitro data demonstrated a stimulatory effect of low pH on intestinal HCO(3)(-) secretion. Thus, both luminal Ca(2+) and H(+) can regulate HCO(3)(-) secretion but the precise mechanisms and their potential interaction are currently unresolved.     

Lipid Absorption Defects in Intestine-specific Microsomal Triglyceride Transfer Protein and ATP-binding Cassette Transporter A1-deficient Mice

We have previously described apolipoprotein B (apoB)-dependent and -independent cholesterol absorption pathways and the role of microsomal triglyceride transfer protein (MTP) and ATP-binding cassette transporter A1 (ABCA1) in these pathways. To assess the contribution of these pathways to cholesterol absorption and to determine whether there are other pathways, we generated mice that lack MTP and ABCA1, individually and in combination, in the intestine. Intestinal deletions of Mttp and Abca1 decreased plasma cholesterol concentrations by 45 and 24%, respectively, whereas their combined deletion reduced it by 59%. Acute cholesterol absorption was reduced by 28% in the absence of ABCA1, and it was reduced by 92–95% when MTP was deleted in the intestine alone or together with ABCA1. MTP deficiency significantly reduced triglyceride absorption, although ABCA1 deficiency had no effect. ABCA1 deficiency did not affect cellular lipids, but Mttp deficiency significantly increased intestinal levels of triglycerides and free fatty acids. Accumulation of intestinal free fatty acids, but not triglycerides, in Mttp-deficient intestines was prevented when mice were also deficient in intestinal ABCA1. Combined deficiency of these genes increased intestinal fatty acid oxidation as a consequence of increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and carnitine palmitoyltransferase 1α (CPT1α). These studies show that intestinal MTP and ABCA1 are critical for lipid absorption and are the main determinants of plasma and intestinal lipid levels. Reducing their activities might lower plasma lipid concentrations.     

Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione

Menadione (MEN) inhibits intestinal calcium absorption by a mechanism not completely understood. The aim of this work was to find out the role of mitochondria in this inhibitory mechanism. Hence, normal chicks treated with one i.p. dose of MEN were studied in comparison with controls. Intestinal calcium absorption was measured by the in situ ligated intestinal segment technique. GSH, oxidoreductase activities from the Krebs cycle and enzymes of the antioxidant system were measured in isolated mitochondria. Mitochondrial membrane potential was measured by a flow cytometer technique. DNA fragmentation and cytochrome c localization were determined by immunocytochemistry. Data indicate that in 30 min, MEN decreases intestinal Ca(2+) absorption, which returns to the control values after 10 h. GSH was only decreased for half an hour, while the activity of malate dehydrogenase and alpha-ketoglutarate dehydrogenase was diminished for 48 h. Mn(2+)-superoxide dismutase activity was increased in 30 min, whereas the activity of catalase and glutathione peroxidase remained unaltered. DNA fragmentation and cytochrome c release were maximal in 30 min, but were recovered after 15 h. In conclusion, MEN inhibits intestinal Ca(2+) absorption by mitochondrial dysfunction as revealed by GSH depletion and alteration of the permeability triggering the release of cytochrome c and DNA fragmentation.     

Redistribution of intestinal microcirculatory oxygenation during acute hemodilution in pigs.

Acute normovolemic hemodilution (ANH) compromizes intestinal microcirculatory oxygenation; however, the underlying mechanisms are incompletely understood. We hypothesized that contributors herein include redistribution of oxygen away from the intestines and shunting of oxygen within the intestines. The latter may be due to the impaired ability of erythrocytes to off-load oxygen within the microcirculation, thus yielding low tissue/plasma Po(2) but elevated microcirculatory hemoglobin oxygen (HbO(2)) saturations. Alternatively, oxygen shunting may also be due to reduced erythrocyte deformability, hindering the ability of erythrocytes to enter capillaries. Anesthetized pigs underwent ANH (20, 40, 60, and 90 ml/kg hydroxyethyl starch; ANH group: n = 10; controls: n = 5). We measured systemic and mesenteric perfusion. Microvascular intestinal oxygenation was measured independently by remission spectrophotometry [microcirculatory HbO(2) saturation (muHbO(2))] and palladium-porphyrin phosphorescence quenching [microcirculatory oxygen pressure in plasma/tissue (muPo(2))]. Microcirculatory oxygen shunting was assessed as the disparity between mucosal and mesenteric venous HbO(2) saturation (HbO(2)-gap). Erythrocyte deformability was measured as shear stress-induced cell elongation (LORCA difractometer). ANH reduced hemoglobin concentration from 8.1 to 2.2 g/dl. Relative mesenteric perfusion decreased (decreased mesenteric/systemic perfusion fraction). A paralleled reduction occurred in mucosal muHbO(2) (68 +/- 2 to 41 +/- 3%) and muPo(2) (28 +/- 1 to 17 +/- 1 Torr). Thus the proposed constellation indicative for oxygen off-load deficits (sustained muHbO(2) at decreased muPo(2)) did not develop. A twofold increase in the HbO(2)-gap indicated increasing intestinal microcirculatory oxygen shunting. Significant impairment in erythrocyte deformability developed during ANH. We conclude that reduced intestinal oxygenation during ANH is, in addition to redistribution of oxygen delivery away from the intestines, associated with oxygen shunting within the intestines. This shunting appears to be not primarily caused by oxygen off-load deficit but rather by oxygen/erythrocytes bypassing capillaries, wherein a potential contributor is impaired erythrocyte deformability.     

Histamine release by pharmacological agents in the absence of external free Ca2+

The involvement of extracellular free Ca2+ in histamine release was investigated in rat peritoneal mast cells. Incubation of non-antigenized cells in a media with high extracellular potassium did not increase histamine release. Secretion induced by A23187 and compound 48/80 in the presence of Ca2+ requires metabolic energy. In the absence of external free Ca2+ (2.5 microM) histamine release induced by A23187 is reduced but not abolished. Secretion induced by compound 48/80 is independent of extracellular Ca2+. These results lead us to suggest that mast cell plasma membranes probably lack voltage-gated Ca2+ channels and that external Ca2+ may not be an absolute requisite for histamine secretion.