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W Rummel

Publications and source records attributed to W Rummel.

At least 55 records · Page 3Linked to original sources
PubMed1986

The role of the paracellular pathway in the net transport of calcium across the colonic mucosa.

Concentration dependent calcium fluxes across the colon descendens of the rat were measured in a modified Ussing chamber. Mucosa (m) to serosa (s) calcium flux showed a saturable component, whereas s to m calcium flux was linearly related to the calcium concentration. At low calcium concentrations net absorption and at concentration above 2.5 mmol/l net secretion of calcium was observed. The results obtained from the unidirectional calcium fluxes when clamping the transepithelial electrical potential agree well with those of the concentration dependence of the calcium fluxes: Only m to s flux has a voltage independent component. Calcium s to m movement is totally voltage dependent. Diffusional s to m calcium flux is greater than the diffusional fraction of the m to s calcium flow. Dexamethasone, known to stimulate water absorption in the colon descendens by an activation of sodium transport, had no effect on the cellular mediated m to s calcium transport but significantly increased paracellular s to m flux parallel to that of the extracellular marker mannitol. This increase in paracellular s to m calcium and mannitol flux was completely abolished by amiloride, which is known to suppress the dexamethasone-induced stimulation in sodium and water absorption. The results demonstrate that the increased paracellular s to m calcium and mannitol flow is oppositely directed to the dexamethasone-induced net fluid movement as it could be expected on the basis of Ussing's "anomalous solvent drag" effect.

Amiloride↗
PubMed1986

Trans- and paracellular calcium transport across the colonic mucosa after short- and long-term treatment with 1,25-dihydroxyvitamin D3.

The electrical parameters and the unidirectional fluxes of 45Ca and 3H-mannitol were measured in preparations of rat colon descendens freed from the muscularis externa and mounted in a modified Ussing-chamber. Two criteria were used to differentiate between changes in the trans- and the paracellular calcium transport after treatment with 1,25(OH)2D3: the fluxes of the simultaneously measured 3H-mannitol as a paracellular marker; the 45Ca fluxes in preparations with clamped potentials. After a short-time (6 h) pretreatment by s.c. administration of 1,25(OH)2D3 (250 ng kg-1) in normal rats the mucosa (m) to serosa (s) 45Ca flux under short circuit conditions increased about 65%, whereas the electrical parameters and the 3H-mannitol fluxes remained unchanged. In clamped epithelia the PD-independent m to s 45Ca flux was increased, whereas the PD-dependent flux remained unchanged. In contrast, after long-time (4 days) induction by 1,25(OH)2D3 the m to s 45Ca flux increased under short circuit conditions by about 100% and the m to s 3H-mannitol flux increased by 50%, PD and Isc decreased by more than 60%, whereas tissue resistance was the same, in clamped epithelia the calculated PD-independent, transcellular m to s 45Ca flux was 2.4 times and the PD-dependent, paracellular 45Ca-flux was 1.9 times higher than in controls, whereas the s to m 45Ca flux remained unchanged. On the basis of the relevant references the following conclusions were drawn: after short-time exposure to 1,25(OH)2D3 only the PD-dependent, transcellular m to s calcium transport is increased; this is probably due to a liponomic effect of 1,25(OH)2D3 at the brush border membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Mucosal plexus and electrolyte transport across the rat colonic mucosa.

Histological and functional studies were performed on a preparation of rat colonic mucosa from which the myenteric and submucosal plexus were removed. This preparation, referred to as the mucosa preparation, was used to investigate the potential influence of the mucosal plexus on electrolyte transport. Two neuropharmacologically active agents were used: sea anemone toxin (ATX II) to stimulate the fibres of the mucosal plexus and tetrodotoxin (TTX) to block the fibres of the mucosal plexus. The morphology of the neuronal network of the mucosal plexus was visualized after the epithelium was removed and whole mount preparations of the lamina propria and circular muscle layer of muscularis mucosae were stained histochemically for acetylcholinesterase activity. Several levels of organization within the mucosal plexus were seen. Each crypt is encircled by a thin bundle of fibres near the top. These thin fibres connect with thicker bundles of fibres that encircle groups of two to five crypts in a broad band. These bundles of fibres are in turn connected to larger bundles of fibres which lie in a flat plane just below the crypts along the circular muscle layer of muscularis mucosae. In addition perikarya and ganglia were revealed within the mucosal plexus. The base-line net transport of Na+ and Cl- across the mucosa preparation was completely inhibited by ATX II (10(-6) M). This effect of ATX II on net Na+ and Cl- transport was accompanied with an increase in the short-circuit current (Isc), transmural conductance, and open-circuit potential difference across the mucosa preparation. The effect of ATX II on Isc was dose dependent with a half-maximal effective concentration at 5 X 10(-8) M-ATX II and a maximal effective concentration of 10(-7) M. ATX II was effective only when added to the serosal solution. Net Na+ and Cl- transport was restored by TTX (10(-6) M) to base-line values in ATX II-treated tissue. In addition the value of all three electrical parameters rapidly returned to the values measured before the addition of ATX II. TTX was effective in antagonizing the effects of ATX II only when added to the serosal solution. The results suggest that the regulation of electrolyte transport across the epithelium is at least one function of the mucosal plexus. Stimulation of the neurones within the mucosal plexus leads to the inhibition of electrolyte absorption.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Mechanistic basis of alterations in mucosal water and electrolyte transport.

Diarrhoea can, in principle, result from the stimulation of secretion, the inhibition of absorption, or both. In practice, it is the simultaneous stimulation of secretion and inhibition of absorption that has most frequently been observed. The majority of substances affecting the intestine fall into two categories, those stimulating secretion and inhibiting absorption and those having the opposite effects. It is therefore important to understand both the mechanisms of secretion and the mechanisms of absorption. In this chapter, the basic cellular mechanisms by which water and electrolytes are actively absorbed and secreted in the small and large intestine have been presented. The steps at which these mechanisms are thought to be regulated by one or all of the three potential intracellular mediators, cAMP, cGMP and Ca++, have been indicated. It is hoped that an understanding of these basic cellular mechanisms will aid in understanding the pathophysiological conditions of diarrhoea described in the following chapters.

Adrenal Cortex Hormones↗
PubMed1985

Mucosal iron binding proteins and the inhibition of iron absorption by endotoxin.

The uptake of iron from a tied off jejunal segment into the body after the injection of a 59Fe labeled test dose was decreased after the administration of endotoxin by about 80% in both normal and iron deficient animals.--In the iron deficient group the distribution of 59Fe in the cytosol fraction of jejunal mucosa between transferrin and ferritin was determined chromatographically; the amount of 59Fe in the ferritin fraction increased remarkably after the endotoxin treatment and the ratio of both was changed in favor of ferritin.--It is hypothesized that the association of the diversion of iron to the mucosal ferritin with the decrease of the transport of iron into the blood caused by endotoxin might be the consequence of abnormal oxidations in the mucosa measured by others in liver tissue.

Absorption↗
PubMed1985

Influence of phosphate, sulfonic, and sulfamic acids on sulfoconjugate release in the vascularly perfused mouse small intestine.

An in vitro vascularly and luminally perfused preparation of the murine small intestine was used to investigate the interference of isethionate, cyclamate and HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) with the luminal transport of the isoprenaline-sulfoconjugate as well as with the basolateral transport of naphthol-sulfoconjugate. The sulfonates and sulfamates when administered from the luminal as well as from the contraluminal side of the epithelium inhibited the transport of isoprenaline-sulfoconjugate. Inhibition of the naphthol-sulfoconjugate transport across the contraluminal epithelial membrane was less pronounced, but a countertransport phenomenon could be induced with cyclamate in the vascular medium. The presence of phosphate at the luminal side is essential for the transport of the isoprenaline-sulfoconjugate across the luminal membrane. This is not the case for bicarbonate. The conclusion is drawn that different transport systems for sulfoconjugates exist in the luminal and in the contraluminal membranes of the intestinal mucosa, which can be inhibited by structurally related compounds. The luminal transport system can be activated from the luminal side by phosphate.

Animals↗
PubMed1985

Submucosal plexus and electrolyte transport across rat colonic mucosa.

Electrolyte transport across two preparations of mucosa from rat colon descendens was compared to determine what influence the submucosal plexus has on electrolyte transport. One preparation consisted of the mucosa, muscularis mucosae, and the submucosal tissue and is referred to as the mucosa-submucosa preparation. The second preparation obtained by further blunt dissection of the mucosa-submucosa preparation consisted of only the mucosa and the circular muscle layer of muscularis mucosae and is referred to as the mucosa preparation. Histological studies showed that the submucosal tissue and the longitudinal layer of muscularis mucosae could be removed leaving only the mucosa and the circular layer of muscularis mucosae. The extensive neuronal network of the submucosa was shown when the submucosal tissue and longitudinal muscle layer of muscularis mucosae, which were removed, were stained histochemically for acetylcholinesterase activity. Both the mucosa-submucosa and mucosa preparations absorbed Na+ and Cl- when short-circuited. However, Na+ and Cl- absorption were significantly higher in the mucosa preparation. The increase in Na+ and Cl- transport in the mucosa preparation was accompanied with a decrease in the short-circuit current (Isc), the open-circuit potential difference (p.d.) and the transmural tissue conductance (Gt) when compared to the mucosa-submucosa preparation. Tetrodotoxin (TTX), a neurotoxin which blocks specifically the propagation of action potentials in excitable tissues, dose-dependently decreased Isc and p.d. in the mucosa-submucosa preparation when added to the serosal solution. The half-maximal effective concentration of TTX was 5 nM and maximal effective concentration 100 nM. TTX (1 microM) had no effect on Isc or p.d. when added to the mucosal solution. The decrease in Isc and p.d. caused by TTX in the mucosa-submucosa preparation was accompanied with an increase in Na+ and Cl- absorption. TTX caused only a small decrease in Isc and p.d. in the mucosa preparation. However, there was no measurable change in Na+ and Cl- transport in the mucosa preparation. The results suggest that spontaneously active neurones from the submucosal plexus have an inhibitory influence on the mucosa. Physical removal of the submucosal plexus or pharmacological blockade of the neurones within the mucosa-submucosa preparation by TTX led to enhanced absorption, suggesting that the set point of the mucosa for electrolyte transport is at or near a maximal absorptive state. Regulation or modulation of the mucosa may therefore occur by mechanisms that lower this set point, causing an inhibition of absorption of electrolytes.

Animals↗
PubMed1984

Depression by morphine and levorphanol of activity in sympathetic nerve fibres in anaesthetized rats.

In urethane-anesthetized rats, the effects of intravenous injections of morphine, levorphanol, dextrorphan, pentazocine and naloxone were studied studied on the activity in nerve fibres of the cervical sympathetic trunk, and on mean arterial blood pressure and heart rate. Impulse frequency in sympathetic nerve fibres was recorded with tungsten microelectrodes and proved to be more sensitive to drug action than blood pressure or heart rate. Morphine 1 and 2 mg/kg dose dependently reduced sympathetic impulse frequency, blood pressure and heart rate; morphine 0.5 mg/kg was ineffective. Levorphanol 1 and 2 mg/kg dose dependently reduced sympathetic impulse frequency and blood pressure but did not affect heart rate. Dextrorphan (the dextro-isomer of levorphanol) 2 and 4 mg/kg had no effect on the parameters tested. Pentazocine 3 and 6 mg/kg did not cause a consistent change in sympathetic impulse frequency, blood pressure and heart rate. Naloxone 0.2 mg/kg abolished the depressant effects of morphine and levorphanol and, when given alone, increased sympathetic impulse frequency. Naloxone 1 mg/kg increased blood pressure but did not affect heart rate. It is concluded that morphine can reduce blood pressure and heart rate by causing opiate-specific central sympathetic depression.

Adrenergic Fibers↗
PubMed1984

Vectorial release of sulfoconjugates in the vascularly perfused mouse small intestine.

Sulfoconjugates are formed from various xenobiotics and drugs in the vascularly perfused mouse small intestine. They can be grouped according to the sidedness of their release from the epithelium. Conjugates of paracetamol and salicylamide, like 1-naphthol-sulfate, are released exclusively into the vascular medium, whereas those of diethylstilbestrol, ethinyl-estradiol and isoprenaline appear only in the luminal perfusion medium. It is concluded from these results that selective anion transport systems for sulfoconjugates exist in the brush-border membrane as well as in the basolateral membrane of the enterocyte.

Animals↗
PubMed1984

Effects of vasopressin on electrolyte transport across isolated colon from normal and dexamethasone-treated rats.

Vasopressin enhanced the absorption of Na+ and Cl- across the short-circuited colon descendens from normal rats. This effect of vasopressin results from an increase in the mucosal to serosal movement of Na+ and Cl- and a decrease in the serosal to mucosal movement of Cl- and was accompanied with a decrease in the short-circuit current (ISC). Neither the base-line absorption of Na+ and Cl-, the vasopressin-induced increase in Na+ and Cl- absorption nor the decrease in ISC were inhibited by amiloride in the colon from normal rats. Colon descendens from rats treated for 3 days with dexamethasone had remarkably higher transmural potential difference (p.d.), tissue conductance (Gt) and ISC. The absorption of Na+ across the short-circuited colon descendens from dexamethasone-treated rats was increased 3-fold when compared to colon from normal rats. The absorption of Cl- in normal rats was reversed to Cl- secretion in treated rats. Amiloride rapidly and reversibly decreased the p.d., Gt and ISC in colon from dexamethasone-treated rats. The transport of Na+ was nearly completely inhibited by amiloride in treated rats. In contrast to its enhancing effects on Na+ absorption in colon from normal rats vasopressin did not enhance Na+ absorption in colon from dexamethasone-treated rats. This enhancement of Cl- absorption by vasopressin was retained in colon from treated rats. This enhancement of Cl- transport was due solely to a decrease in the serosal to mucosal movement of Cl- and was accompanied with a decrease in ISC and Gt. The results support the hypothesis that vasopressin causes inhibition of the electrogenic secretion of Cl- in colon from dexamethasone-treated rats. Furthermore, the results suggest that the increase in the mucosal to serosal movement of Na+ and Cl- and the decrease in the serosal to mucosal movement of Cl- in colon from normal rats are caused by independent effects of vasopressin.

Amiloride↗
PubMed1983

Conjugation of 1-naphthol and transport of 1-naphthol-conjugates in the vascularly perfused small intestine of the mouse.

A method is described which allows the simultaneous vascular and luminal perfusion of the murine small intestine. This preparation was used for the investigation of 1-naphthol conjugation in the gut and the sidedness of conjugate release. The viability of this preparation can be maintained for more than 1 hr as indicated by morphological controls, measurement of tissue metabolism and the transport of 3-O-methyl-glucose against a concentration gradient. When 100 microM 1-naphthol was administered on the luminal side, it was conjugated at a constant rate, yielding 1-naphthyl-glucuronide and 1-naphthyl-sulfate in a molar ratio of 1:2. Both metabolites were excreted into the blood at the contraluminal side of the epithelium. The results are discussed with respect to the sidedness of intestinal transport systems for anionic conjugates of xenobiotics and drugs.

3-O-Methylglucose↗
PubMed1983

Forskolin induced chloride secretion across the isolated mucosa of rat colon descendens.

The effects of forskolin, a diterpene reported to stimulate adenylate cyclase, on electrolyte transport across the isolated colonic mucosa of rat colon descendens were investigated. Forskolin, over a concentration range of 10(-7)-10(-5) M, dose-dependently increased short circuit current (Isc) and transmural potential difference (Vms). The nearly 2-fold increase in Isc and Vms caused by forskolin was accompanied by a small increase in transmural conductance (Gt). The effects of forskolin were rapid and completely reversible without any loss in tissue sensitivity. Forskolin (5 X 10(-6) M) inhibited the absorption of Na+ and reversed Cl- absorption to secretion. These effects were due to an inhibition of the mucosal-to-serosal fluxes of Na+ and Cl-. Ion substitution experiments revealed that the effects of forskolin were both Na+ and Cl- dependent and these ions were required in the serosal solution. Furosemide (10(-4) M) as well as scilliroside (10(-4) M) reversed and prevented the increase in Isc caused by forskolin. Adenylate cyclase activity in homogenates of colonic mucosa was increased 3-fold by forskolin. These results with rat colon are compared with those reported for rabbit colon and ileum and the mechanism of cyclic-AMP induced Cl- secretion in these epithelia is discussed.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Differentiation of secretagogue drugs by chlorpromazine in rat intestine in vivo.

The effect of chlorpromazine (CPZ) on passive epithelial permeability and net fluid movement induced by secretagogues was tested in the rat intestine in vivo. CPZ, in a dose of 20 mg/kg intramuscularly, did not alter colonic permeability either in control conditions or during increased permeability caused by deoxycholic acid (DOC) or bisacodyl. Fluid secretion induced by cholera toxin and theophylline was strongly reduced by CPZ. The effects of oxyphenisatin and bisacodyl were only slightly but significantly inhibited by CPZ, whereas the action of DOC was unaffected. It is concluded, that the increase of the epithelial permeability is the main reason for the augmented fluid secretion caused by DOC. Bisacodyl and oxyphenisatin seem to act partly via an increase in permeability and to some degree via an induction of an active secretory process.

Animals↗
PubMed1983

Influence of vasopressin and calcium on electrolyte transport across isolated colonic mucosa of the rat.

Vasopressin enhanced the absorption of water and Na+ across everted sacs of rat colon descendens but had no effect on absorption across the colon ascendens. The short-circuit current (Isc) and open-circuit potential difference (p.d.) across the colon descendens were dose-dependently decreased by vasopressin. Isc and p.d. across the colon ascendens were not altered by vasopressin. In the colon descendens the decrease in Isc and p.d. was significant at 1 microu. vasopressin/ml and reached a maximum at 1 mu./ml. Propranolol and phentolamine or naloxone did not alter the decrease in Isc and p.d. to a submaximal dose of vasopressin. Vasopressin increased the mucosal to serosal flux of Na+ and Cl- and decreased the serosal to mucosal flux of Cl- across short-circuited colon descendens. Consequently these changes increased the net flux of Na+ and Cl-. Adenylate cyclase activity in homogenates of the colon descendens was not altered by vasopressin. Omission of Ca2+ from the serosal bathing solution reversibly decreased Isc and p.d. and increased Na+ and Cl- absorption across the colon descendens in a similar way as did vasopressin. The results suggest that the effect of vasopressin on the colon descendens may be due to a decrease in intracellular Ca2+ activity.

Adenylyl Cyclases↗
PubMed1983

Effect of deoxycholate on the perfused rat colon. Concentration dependence of the effect on net fluid and electrolyte transfer and the correlation with paracellular permeability.

We reexamined the question whether the deoxycholate-evoked alteration of net transfer of fluid and electrolytes is primarily caused by active secretion or paracellular filtration. In the in vivo perfused rat colon, deoxycholate caused a dose-related increase in 51Cr-EDTA clearance proportional to the rate of fluid, sodium, and chloride secretion. These increases of fluid production and epithelial permeability were reversible and showed the same time dependence. Potassium, however, was already maximally secreted at the lowest deoxycholate concentration (1 mmol/l). This study supports the hypothesis that the secretion of fluid in the deoxycholate-treated colon is quantitatively determined by the increase of the paracellular permeability.

Animals↗
PubMed1983

Is the secretagogue effect of deoxycholic acid mediated by the adenylate cyclase-cAMP system.

The role of the adenylate cyclase (Ac)-cAMP system in mediating deoxycholic acid (DOC)-induced fluid secretion was studied in the rat jejunum and colon in vivo using the AC inhibitor, RMI 12 330 A. A potent inhibitory effect of RMI 12 330 A on fluid secretion induced by cholera toxin was demonstrated in ligated rat jejunal loops. On the contrary, the changes of fluid movement in jejunal and colonic loops caused by DOC could not be influenced by RMI 12 330 A, and mucosal cAMP levels of colonic loops were not increased. Colonic mucosal permeability estimated by the 14C-erythritol clearance increased significantly during a 45-min exposure to 3 mmol DOC, and was not affected by RMI 12 330 A. These results do not support the theory that the AC-cAMP system plays an important role in DOC-induced intestinal fluid secretion and suggest that an increase in mucosal permeability is the predominant factor responsible for the secretagogue effect.

Adenylyl Cyclase Inhibitors↗
PubMed1983

The significance of transferrin for intestinal iron absorption.

A mechanism is proposed by which apotransferrin is secreted from mucosal cells, loaded with iron in the intestinal lumen, and then the intact complex is taken into the cell. Within the cell, iron is released and transferred to the blood stream, whereas iron-free transferrin returns to the brush border to be recycled. We have investigated this hypothesis by measuring intestinal absorption of radioiron and 125I-labeled plasma transferrin using tied-off gut segments in normal and iron-deficient rats. There was no absorption of diferric transferrin from the ileum, but high absorption from the duodenum and jejunum segments. Jejunal absorption occurred as a function of the dose offered and showed saturation kinetics. In normal animals, 4 micrograms of the 50 micrograms of transferrin iron was absorbed over 1 hr. In iron-deficient animals, mean values as high as 13 micrograms were observed. Radioiron content of the jejunal mucosa bore a linear relationship to the dose administered and was inversely proportional to the amount of iron entering the plasma. Recycling of transferrin was indicated by the presence of labeled apotransferrin in the lumen, first observed between 15 and 60 min after the injection of diferric transferrin. A high resistance of diferric and apotransferrin to proteolytic degradation within the gut lumen was demonstrated. Comparative studies with lactoferrin and ferritin disclosed poor availability of their iron for absorption. The small amount that was absorbed did not relate to the iron status of the recipient animal. These studies support the role of mucosal transferrin as a shuttle protein for iron absorption.

Anemia, Hypochromic↗