Effects of different metabolites of vitamin D3 and of calcium concentration on the intestinal absorption of strontium]

The effect of calcium concentration and vitamin B3 25 OHD3 and 1.25 diOHD3 upon intestinal strontium transport was studied in vitamin D deficient rats with duodenal perfusion in situ. When the calcium concentration was increased, the strontium passive absorption was decreased. The vitamin D3 and its derivatives increased intestinal strontium transport significantly and this increment was not modified by calcium. In our experiment, calcium is competitive with strontium only in passive absorption.     

Prolactin stimulates the L-type calcium channel-mediated transepithelial calcium transport in the duodenum of male rats

Elevated plasma levels of prolactin (PRL) have been reported in several physiological and pathological conditions, such as lactation, prolactinoma, and dopaminergic antipsychotic drug uses. Although PRL is a calcium-regulating hormone that stimulates intestinal calcium absorption in lactating rats, whether PRL is capable of stimulating calcium absorption in male rats has been elusive. Herein, the transepithelial calcium transport and electrical characteristics were determined in ex vivo duodenal tissues of male rats by Ussing chamber technique. We found that PRL receptors were abundantly present in the basolateral membrane of the duodenal epithelial cells. PRL (200–800 ng/mL) markedly increased the active duodenal calcium transport in a dose-dependent fashion without effect on the transepithelial resistance. The PRL-enhanced active duodenal calcium transport was completely abolished by L-type calcium channel blocker (nifedipine) as well as inhibitors of the major basolateral calcium transporters, namely plasma membrane Ca²⁺-ATPase and Na⁺/Ca²⁺ exchanger. Several intracellular mediators, such as JAK2, MEK, PI3K and Src kinase, were involved in the PRL-enhanced transcellular calcium transport. Moreover, PRL also stimulated the paracellular calcium transport in the duodenum of male rats in a PI3K-dependent manner. In conclusion, PRL appeared to be a calcium-regulating hormone in male rats by enhancing the L-type calcium channel-mediated transcellular and the paracellular passive duodenal calcium transport. This phenomenon could help restrict or alleviate negative calcium balance and osteoporosis that often accompany hyperprolactinemia in male patients.     

Chronic metabolic acidosis stimulated transcellular and solvent drag-induced calcium transport in the duodenum of female rats

Chronic metabolic acidosis results in a negative calcium balance as a result of bone resorption and renal calcium loss. However, reports on the changes in intestinal calcium transport have been controversial. The present investigation therefore aimed to study the effects of chronic metabolic acidosis induced by 1.5% NH(4)Cl administration on the three components of duodenal calcium transport, namely, solvent drag-induced, transcellular active, and passive paracellular components, in rats using an in vitro Ussing chamber technique. The relative mRNA expression of genes related to duodenal calcium transport was also determined. We found that 21-day chronic metabolic acidosis stimulated solvent drag-induced and transcellular active duodenal calcium transport but not passive paracellular calcium transport. Our results further demonstrated that an acute direct exposure to serosal acidic pH, in contrast, decreased solvent drag-induced calcium transport in a pH-dependent fashion but had no effect on transcellular active calcium transport. Neither the transepithelial resistance nor duodenal permeability to Na(+), Cl(-), and Ca(2+) via the passive paracellular pathway were altered by chronic metabolic acidosis, suggesting that widening of the tight junction and changes in the charge-selective property of the tight junction did not occur. Thus the enhanced duodenal calcium transport observed in chronic metabolic acidosis could have resulted from a long-term adaptation, possibly at the molecular level. RT-PCR study revealed that chronic metabolic acidosis significantly increased the relative mRNA expression of duodenal genes associated with solvent drag-induced transport, i.e., the beta(1)-subunit of Na(+)-K(+)-ATPase, zonula occludens-1, occludin, and claudin-3, and with transcellular active transport, i.e., transient receptor potential vanilloid family Ca(2+) channels 5 and 6 and plasma membrane Ca(2+)-ATPase isoform 1b. Total plasma calcium and free ionized calcium and magnesium concentrations were also increased, whereas serum parathyroid hormone and 1alpha,25-dihydroxyvitamin D(3) levels were not changed. The results indicated that 21-day chronic metabolic acidosis affected the calcium metabolism in rats partly through enhancing the mRNA expression of crucial duodenal genes involved in calcium absorption, thereby stimulating solvent drag-induced and transcellular active calcium transport in the duodenum.     

Stereological studies on the ultrastructural markers of renal tubular transport during accelerations acting along the +Gz axis

The study was carried out on rats. Electron micrographs of the kidney obtained under +Gz accelerations were analysed. Using stereological methods the estimation of ultrastructural markers of active transport (mitochondria energy state), and passive transport (intercellular spaces and basal infolded channels) was performed in the proximal and distal tubules. The results obtained indicated that during the actions of accelerations active tubular transport was impaired as reflected by a lowering of mitochondrial energy states (similar to condensed) in the proximal and distal tubules. Widening of intercellular spaces and basal infolded channels was also observed, which suggests fluid stasis and thus impairment of passive transport.     

Changes in autoregulation of coronary blood flow in rats with various sensitivity to stress

The purpose of work: study of a role of endothelial nitric oxide in development of stress-induced changes in autoregulation of coronary blood flow in rats with various types of behaviour. The experiments were performed on isolated hearts of female-rats, in the "open field" test, depending on the type of impelling and searching activity of animals subdivided into two groups: "active" and "passive". After a 6-hour immobilization stress only in "passive" rats an increase of volumetric velocity of coronary flow; a decrease of an autoregulation index, coronary reserve against the background of intravascular pressure reduction, were found out. The blockade of nitric oxide synthesis in this group completely eliminated the stress-induced decrease of coronary vascular tone and essentially limited the caused by stress dissociation of coronary flow and the contractility function of the myocardium. In blood plasma of "passive" animals the nitrite/nitrate contents was by 55% more than of the "active" rats. After the transferred stress, in "passive" animals the nitrite/nitrate concentration in blood plasma increased by 29% and in "active" rats--by 136%; the absolute values, however, did not differ between the groups. Thus the autoregulation of coronary flow seems to be subject to action of stress in the rats showing a "passive" type of behaviour in the test "open field", and practically does not change in "active" animals; secondly, in spite of the fact that the stress-induced amplification of NO-producing function andothelium of coronary blood vessels is stereotyped in different rats, in "passive" rats, apparently, sensitivity of coronary vessels to nitric oxide is higher than at "active" those.     

The delayed effects of systemic circulatory arrest on the free-radical processes in the brain structures of rats with different types of behavior in the emotional resonance test]

Male Wistar rats with different types of behavior in "emotional resonance" test ("active" and "passive") were studied one week after the global ischemia induced by cardiac arrest. Recovery of some physiological functions as well as free-radical-mediated processes and NO-synthase activity were studied in cerebral structures and blood serum. The "open-field" behavior normalized more rapidly in the "active" rats than in the "passive" ones, though the time course of the neurologic deficit compensation did not differ in these groups. A decrease in superoxide scavenging activity and in the content of 2-thiobarbituric acid-reactive material was revealed in the cerebral structures of both "active" and "passive" rats. Increased levels of free-radical generation in the hippocampus of the "passive" rats and in the cerebellum of the "active" rats were found. Higher NO-synthase activity was demonstrated in the cerebellum of the "passive" rats. Taken together, these data suggest that there are specific patterns of free-radical-mediated processes in the brain of rats with different types of behavior in "emotional resonance" test.     

The relative roles of passive surface forces and active ion transport in the modulation of airway surface liquid volume and composition

Two hypotheses have been proposed recently that offer different views on the role of airway surface liquid (ASL) in lung defense. The "compositional" hypothesis predicts that ASL [NaCl] is kept low (<50 mM) by passive forces to permit antimicrobial factors to act as a chemical defense. The "volume" hypothesis predicts that ASL volume (height) is regulated isotonically by active ion transport to maintain efficient mechanical mucus clearance as the primary form of lung defense. To compare these hypotheses, we searched for roles for: (1) passive forces (surface tension, ciliary tip capillarity, Donnan, and nonionic osmolytes) in the regulation of ASL composition; and (2) active ion transport in ASL volume regulation. In primary human tracheobronchial cultures, we found no evidence that a low [NaCl] ASL could be produced by passive forces, or that nonionic osmolytes contributed substantially to ASL osmolality. Instead, we found that active ion transport regulated ASL volume (height), and that feedback existed between the ASL and airway epithelia to govern the rate of ion transport and volume absorption. The mucus layer acted as a "reservoir" to buffer periciliary liquid layer height (7 microm) at a level optimal for mucus transport by donating or accepting liquid to or from the periciliary liquid layer, respectively. These data favor the active ion transport/volume model hypothesis to describe ASL physiology.     

Effect of functional loading on the operation of the active transport system for organic acids in the proximal kidney tubules of rats after unilateral nephrectomy and in the early postnatal period

The influence of a prolonged introduction of exogenic organic acid penicillin (that is functional loading) on the level of accumulation of an anionic dye (fluorescein) in renal proxima tubules was studied after unilateral nephrectomy and early postnatal period. Injection of penicillin 2 days after unilateral nephrectomy slowly increased Na-independent and strongly increased Na-dependent component of active fluorescein transport in renal proximal tubules of randombred, but strongly decreased both Na-independent and Na-dependent transport in renal tubules of the Campbell rats. When newborn random-bred, Wistar and Campbell rats were pretreated with penicillin, we obtained a slow increase in Na-independent and a strong increase in Na-dependent component of fluorescein transport in renal tubules of random-bred and Wistar rats, but a significant reduction in both Na-independent and Na-dependent transport. It is concluded that the ability for adaptive (or substrate) stimulation of active transport of organic anion in renal proximal tubules is controlled genetically. Adaptive stimulation of organic acid transport in renal tubules referred to in literature as "carried induction", was accomplished apparently by the increase in driving force of the active transport, that is evidently the level of electrochemical Na+-gradient.     

Impaired body calcium metabolism with low bone density and compensatory colonic calcium absorption in cecectomized rats

An earlier study reported that cecal calcium absorption contributes less than 10% of total calcium absorbed by the intestine, although the cecum has the highest calcium transport rate compared with other intestinal segments. Thus, the physiological significance of the cecum pertaining to body calcium metabolism remains elusive. Herein, a 4-wk calcium balance study in cecectomized rats revealed an increase in fecal calcium loss with marked decreases in fractional calcium absorption and urinary calcium excretion only in the early days post-operation, suggesting the presence of a compensatory mechanism to minimize intestinal calcium wasting. Further investigation in cecectomized rats showed that active calcium transport was enhanced in the proximal colon but not in the small intestine, whereas passive calcium transport along the whole intestine was unaltered. Since apical exposure to calcium-sensing receptor (CaSR) agonists similarly increased proximal colonic calcium transport, activation of apical CaSR in colonic epithelial cells could have been involved in this hyperabsorption. Calcium transporter genes, i.e., TRPV6 and calbindin-D(9k), were also upregulated in proximal colonic epithelial cells. Surprisingly, elevated serum parathyroid hormone levels and hyperphosphatemia were evident in cecectomized rats despite normal plasma calcium levels, suggesting that colonic compensation alone might be insufficient to maintain normocalcemia. Thus, massive bone loss occurred in both cortical and trabecular sites, including lumbar vertebrae, femora, and tibiae. The presence of compensatory colonic calcium hyperabsorption with pervasive osteopenia in cecectomized rats therefore corroborates that the cecum is extremely crucial for body calcium homeostasis.     

Na, Cl, and Water Transport by Rat Colon

Segments of the colon of anesthetized rats have been perfused in vivo with isotonic NaCl solutions and isotonic mixtures of NaCl and mannitol. Unidirectional and net fluxes of Na and Cl and the net fluxes of water and mannitol have been measured. Net water transport was found to depend directly on the rate of net Na transport. There was no water absorption from these isotonic solutions in the absence of net solute transport, indicating that water transport in the colon is entirely a passive process. At all NaCl concentrations studied, the lumen was found to be electrically negative to the surface of the colon by 5 to 15 mv. Na fluxes both into and out of the lumen were linear functions of NaCl concentration in the lumen. Net Na absorption from lumen to plasma has been observed to take place against an electrochemical potential gradient indicating that Na is actively transported. This active Na transport has been interpreted in terms of a carrier model system. Cl transport has been found to be due almost entirely to passive diffusion.     

Absorption kinetics for leucine, cycloleucine and alpha-aminoisobutyric acid by rat small intestine in vivo

The intestinal absorption kinetics of three neutral amino acids, leucine, cycloleucine and alpha-aminoisobutyric acid, has been studied in rat jejunum in vivo, with luminal perfusion during successive periods, by measuring the passive component and the active transport. The mass-transfer coefficients of the passive process, are similar for the three amino acids and increase with the perfusion rate. The transport component, obtained from the difference between total absorption and passive diffusion, shows saturation kinetics and also increases with the perfusion rate. The apparent Michaelis constants, Km, and the maximal transport rates for the three amino acids have been determined. The Km values are greater than those reported for in vitro studies, a result imputable to greater thickness of the unstirred layers in vivo and to the unequal signification of the constant in both conditions. Passive flux has proved to be an important component for in vivo absorption, even at low substrate concentrations (1-5 mM), so that its evaluation cannot be neglected for the calculation ot the kinetic constants of the mediated transport.     

c-fos Gene expression in the brain of rats with various exploratory and defensive behavior

Groups of active and passive Wistar rats were revealed in the "open field" and "hole exploration" tests. The pronounced c-fos gene expression was found in different brain structures of rats preliminary subjected to electrodermal stimulation in the "step down" test. Marked differences in c-fos gene expression were observed in brain structures of rats with the active and passive behavior in the "open field", "hole exploration", and "step down" tests. The most pronounced and intensive c-fos gene expression was noticed in the passive rats.     

An analysis of the differences in the effects of diazepam on the EEG of noninbred white rats with high and low expression of anxiolytic action in a conflict situation]

The effects of diazepam (5 mg/kg, i.p.) on the EEG power spectra of the sensorimotor cortex and the dorsal hippocampus were studied in albino rats with different types of conflict behaviour. "Active" rats were characterized by domination of the theta-activity in their background cortical EEG-spectra, "passive" ones--by that of the delta-activity. No differences were revealed in the background hippocampal EEG-spectra. Diazepam produced slowing of the theta-activity and increased the beta-activity in a band of 12-32 Hz in "active" rats and that in a band of 12-16 Hz in "passive" ones. The finding is usefull for studying individual animal sensitivity to drugs effects.     

Hummingbirds rely on both paracellular and carrier-mediated intestinal glucose absorption to fuel high metabolism

Twenty years ago, the highest active glucose transport rate and lowest passive glucose permeability in vertebrates were reported in Rufous and Anna's hummingbirds (Selasphorus rufus, Calypte anna). These first measurements of intestinal nutrient absorption in nectarivores provided an unprecedented physiological foundation for understanding their foraging ecology. They showed that physiological processes are determinants of feeding behaviour. The conclusion that active, mediated transport accounts for essentially all glucose absorption in hummingbirds influenced two decades of subsequent research on the digestive physiology and nutritional ecology of nectarivores. Here, we report new findings demonstrating that the passive permeability of hummingbird intestines to glucose is much higher than previously reported, suggesting that not all sugar uptake is mediated. Even while possessing the highest active glucose transport rates measured in vertebrates, hummingbirds must rely partially on passive non-mediated intestinal nutrient absorption to meet their high mass-specific metabolic demands.     

The characteristics of higher nervous activity and of the brain benzodiazepine system in rats subjected to ethanol exposure in the prenatal period

Exposure to ethanol during pregnancy results in the alternation of 3H-diazepam binding to synaptosomal neocortical membranes from the rat offspring. In male experimental rats, 14 days of age, binding level diminished to 11%. In two-month-old control rats Scatchard plot was biphasic. It has been shown that prenatal exposure to ethanol leads to changes in the nature of binding in two-month-age experimental animals, as compared with the control ones. 3H-diazepam binding changes went along with behavioural deviations. In experimental rats locomotor activity was increased in the "open field" test, passive avoidance conditioned reflex retention was decreased and elaboration parameters of active avoidance conditioned reflex were changed, as compared with the control ones. The data obtained show that higher integrative functions were disturbed by prenatal alcoholization. Correlations between benzodiazepine receptor state and behaviour were studied.     

Cation permeability induced by spermine and polybrene in rat liver mitochondria

The effect of the polybasic substances Polybrene and spermine on the passive and active transport of monovalent cations in mitochondria was studied. These agents were found to stimulate the low amplitude swelling of mitochondria. Volume oscillations were induced by addition of substrate in the presence of spermine. In conditions where weak oscillations were obtained without these substances, oscillations were stimulated and their frequencies increased in the presence of Polybrene and spermine. Their effects were maximal with 100–300 moles spermine per litre and 3–5 mg Polybrene per litre. These results are discussed in relation to an interaction of the agents studied with membrane negative charges which may be important regulators of ion transport.     

Rats with passive coping strategy have average,but not low social range

Social ranks were determined in rats with different degrees of activity-passivity in coping style. The dominance status of rats was assessed by their behavior during social interaction and during competition for food and water. Coping styles were determined during initial trials of acquisition of active avoidance in a two-way shuttle box. Animals with passive behavior in a shuttle box had average scores of social ranks. Both dominant and subordinate rats displayed significantly more active behavior than subdominant animals. In additional experiment, the rats were caged as a one male-one female pairs. Two weeks later, the social ranks of males were determined during agonistic interactions. Males were caged in triads, and corticosterone levels were assayed in blood samples taken from the tail veins during the first five days. The corticosterone level was significantly higher in subdominants than in dominants. There was no significant difference between the dominants and subordinates in corticosterone levels. The obtained evidence suggests the passive coping in subdominant rats, whereas the dominant and subordinate animals were more "active" under aversive stimulation.     

Mechanisms for the intestinal absorption of bile acids

In this review experimental data are summarized which indicate that at least four different transport mechanisms account for net movement of bile acids across the gastrointestinal tract. These are active transport and the passive mechanisms of ionic, nonionic, and micellar diffusion. Of these four, active transport and passive nonionic diffusion are quantitatively of the greatest importance. Active transport is confined to the ileum and probably plays a dominant role in the absorption of conjugated bile acids. Passive nonionic diffusion may occur at any level of the gastrointestinal tract and probably is the major mechanism for the absorption of unconjugated bile acids.     

Alterations in jejunal transport and (Na+-K+)-ATPase in an experimental model of hypoxia in rats

Hypoxia was induced by exposing rats to an atmosphere of 93% N2, 7% O2 for 4-48 hr. The animals became hypoxic as indicated by a decreased blood PaO2 (mean +/- SEM: 48 +/- 10 mm Hg). Hypoxia was accompanied by metabolic acidosis (pH 7.22 +/- 0.02) and decreased serum bicarbonate levels (9.0 +/- 4.0 meq/liter). Hypoxic rats also showed evidence of tissue hypoxia; liver tryptophan oxygenase levels were increased to 21 +/- 2 nmole/min/mg protein. In the hypoxic animals there was decreased jejunal mucosal (Na+-K+)-ATPase activity and an inhibition of active intestinal transport of sodium, glucose, 3-O-methylglucose, galactose, tyrosine, phenylalanine, and glycine as determined by in vivo perfusion studies. Jejunal fructose transport, which has a large passive component, was unaffected by hypoxia. The electrolyte, carbohydrate, and amino acid transport alterations produced by hypoxia were seen in the absence of an effect on jejunal cell number, DNA synthesis, or cell turnover. There was also no evidence of histological or ultrastructural damage. Furthermore, studies with a luminal macromolecular tracer, horseradish peroxidase, indicated that the jejunal lumen-to-blood barrier to macromolecules was also unaltered in these hypoxic animals. In vitro local oxygenation of the jejunum, by bubbling of 95% O2:5% CO2, markedly improved sodium and glucose (but not 3-O-methylglucose) absorption in hypoxic rats and control rats. The (Na+-K+)-ATPase activity of the jejunal mucosa of hypoxic rats was significantly enhanced by the local bubbling of 95% O2:5% CO2. Overall, our data indicate that during relatively mild conditions of hypoxia there is an inhibition of jejunal (Na+-K+)-ATPase activity and related transport processes that is prevented by in situ oxygenation.     

Changes in brain serotonin metabolism and [3H]-serotonin receptor binding during recall of conditioned passive avoidance in rats

The content of serotonin and its metabolite 5-hydroxyindoleacetic acid, monoamine oxidase activity, and [3H]-serotonin radioligand receptor binding were examined in the prefrontal cortex, striatum, amygdala, hippocampus and periaqueductal gray matter at different time after one-trial passive avoidance training of rats. Changes in the serotonergic activity were observed only in rats, which showed retrieval of conditioned passive avoidance response. No serotonergic changes were found immediately and one day after training. Also, there were no changes in trained rats without retrieval of conditioned passive avoidance response or rats with experimental amnesia. The pattern of the involvement of brain structures in the retrieval process was also revealed. [3H]-serotonin binding was decreased in the amygdala, periaqueductal gray matter and striatum, whereas it did not change in the prefrontal cortex and hippocampus. At the same time, the serotonin content in these structures did not differ from that of intact rats. Deamination of serotonin by monoamine oxidase and active transport of 5-hydroxyindoleacetic acid from nerve terminals were increased in the amygdala and periaqueductal gray matter, whereas in the striatum serotonin catabolism was decreased. The obtained differences in serotonin catabo- lism suggest that the decrease in receptor binding of serotonin in these brain structures is provided by different synaptic processes: presynaptic changes in the striatum and postsynaptic receptor changes in the amygdala and periaqueductal gray matter. It is concluded that the decrease in the serotonergic activity in the amygdala and periaqueductal gray matter represents one of the mechanisms activating the emotiogenic system mediating the memory trace retrieval in inhibitory avoidance learning.