G. Nell

Pathway of sodium moving from blood to intestinal lumen under the influence of oxyphenisatin and deoxycholate

Summary1.The transfer of 51CrEDTA and inulinsubstances which are distributed only in the extracellular space-across the rat colonic mucosa in vivo is increased by oxyphenisatin O (3.5 · 10−5 M) and deoxycholate D (3 · 10−3 M).2.O and D do not change the size of the intra- and extracellular fluid compartments of the mucosa as measured with 51CrEDTA from the blood side. The sodium and potassium content of the mucosal tissue is not altered. Therefore the calculated intracellular concentrations of sodium and potassium remain constant.3.The time course of the 22Na uptake into the mucosal epithelium is not influenced by O and D up to 5 min after i.v. injection. The specific activity of sodium, however, in the luminal fluid increases under the influence of O (twofold) and D (fivefold). The uptake of 22Na into the mucosal tissue after administration of 22Na into the intestinal lumen is not changed in presence of O and D.4.We conclude that the net transport of sodium and water from blood to lumen under the influence of O and D occurs mainly via the intercellular way.

Comparative study of the effect of cholera toxin and sodium deoxycholate on the paracellular permeability and on net fluid and electrolyte transfer in the rat colon

Summary1.The effect of deoxycholate and cholera toxin on the transfer of water, sodium, potassium and chloride and on mucosal permeability was studied in perfusion experiments on rat colon in vivo. The influence of both secretagogues on surface morphology was assessed by scanning electron microscopy.2.Deoxycholate turned the absorption of water, sodium and chloride to secretion and enhanced potassium secretion. Cholera toxin induced water and sodium secretion, inhibited chloride absorption and enhanced potassium secretion.3.Deoxycholate increased reversibly the mucosal permeability as measured by the colonic clearance of 51CrEDTA and glucose, whereas cholera toxin decreased the colonic 51CrEDTA clearance.4.Deoxycholate caused protrusion of the luminal cell surface and an increase of exfoliation of epithelial cells. The epithelial continuity was preserved. The only change induced by cholera toxin was an enhanced mucus extrusion.5.Our results are consistent with the view that deoxycholate causes fluid secretion by filtration whereas cholera toxin enhances the secretory activity of the epithelium.

Effect of diphenolic laxatives on Na+-K+-activated ATPase and cyclic nucleotide content of rat colon mucosa in vivo.

Summary1.The effect of bisacodyl and oxyphenisation on the Na+−K+- and Mg2+-activated ATPase and on the mucosa levels of cAMP and cGMP was investigated in transporting ligated loops of the rat colon in acute studies and in chronic feeding experiments.2.The specific activity of the Na+−K+-ATPase was lowered in both types of experiments, concomitantly with a reduction in net sodium absorption. The specific activity of the Mg2+-activated ATPase was unaffected.3.The cAMP content per mg protein was elevated and the cGMP content decreased in the acute experiments in which the effect on transport was most marked. The content of cyclic nucleotides returned to normal within 2 h whereas absorption, Na+−K+-ATPase specific activity and the mucosal potential difference were still significantly depressed at that time. In chronic experiments with bisacodyl, cAMP was not affected and cGMP was increased in colon loops exhibiting reduced absorption.4.The results indicate that the inhibition of the Na+−K+-activated ATPase by diphenolic laxatives may play a role in the inhibition of intestinal fluid absorption caused by these compounds. The increase of cAMP in acute experiments could point to a cAMP-mediated stimulation of secretory processes under this condition.

The hydragogue and laxative effect of the sulfuric acid ester and the free diphenol of 4,4′-dihydroxydiphenyl-(pyridyl-2)-methane

SummaryThe hydragogue and laxative effect of the sulfuric acid ester and the free diphenol of 4,4′-dihydroxydiphenyl-(pyridyl-2)-methane was investigated in rats. In contrast to the free diphenol, the sulfuric acid ester did not show any hydragogue or absorptive inhibiting effect in colon segments of fasted rats, i.e. in the absence of feces in the colon. In fed rats, i.e. in the presence of feces in the colon, however, a dose of the sulfuric acid ester as low as 0.5 mg/segment diminishes the absorption of water significantly. The absorption of water in the rat colon was completely inhibited by 2 mg of the sulfuric acid ester persegment.The sulfuric acid ester is split by microorganisms in the feces of rats and, thus, the free diphenol is liberated. It can be shown by in vitro incubation of the sulfuric acid ester in the presence of rat feces that free diphenol appears. The resulting amount is sufficient to inhibit the absorption of water from the colon.After oral administration the laxative effect of the sulfuric acid ester starts considerably earlier than that of the free diphenol. The reasons for this difference are discussed.

Transfer of sodium and water through isolated rat colonic mucosa under the influence of deoxycholate and oxyphenisatin

Summary1.The influence of oxyphenisatin (OP), a diphenolic laxative, and deoxycholate (DC) on the transfer of sodium and water in an everted sac preparation of stripped rat colon was investigated.2.OP (10−5 M, mucosal side) and DC (3×10−4 M, mucosal side) completely blocked net water and sodium absorption. Net movements from the serosal to the mucosal side could not be induced by higher concentrations of the drugs.3.Unidirectional sodium movements in both directions were increased by OP and DC.4.The effect of DC on the sodium flux from the serosal to the mucosal side was reversible.5.The potassium content of the mucosal epithelium was not changed by DC and OP.6.The integrity of the epithelium, as judged by light microscopy, was not disturbed by either drug under the experimental conditions.7.It is concluded that DC and OP do not interfere with active transport mechanisms but increase the permeability of the epithelium to sodium.

Influence of hydrostatic pressure gradients on net transfer of sodium and water across isolated rat colonic mucosa.

Summary1.The dependence of net transfer of water and sodium on hydrostatic pressure gradients from the serosal to the mucosal side was investigated in everted sacs of the stripped mucosa of the rat colon.2.In the range of 3–20 cm H2O both, net sodium and water transfer were linearly dependent on hydrostatic pressure. The hydraulic permeability coefficient was 1.1 ml per gram dry weight, hour and cm H2O. At a pressure gradient of 5.8 cm H2O the net movement of water from the mucosal to the serosal side ceased. Above this pressure a net movement in the opposite direction occurs. Sodium net movement from the mucosal to the serosal side ceased at 11 cm H2O. The fluid, which appears—driven by higher values of hydrostatic pressure—on the mucosal side, is hypotonic.3.Oxyphenisation increases the hydraulic permeability of the colonic epithelium. The fluid, which appears—driven by the hydrostatic pressure gradient—on the mucosal side, is isotonic.

Independence of the activation of mucus and potassium secretion on the inhibition of sodium and water absorption by deoxycholate in rat colon

SummaryThe dose dependence of the influence of deoxycholic acid (DOC) on fluid and sodium absorption, transmural potential difference (PD), permeability of 14C-erythritol and secretion of potassium and mucus (protein bound hexoses) was measured in the in vivo perfused rat colon. The following results were obtained:1.The threshold concentration for the inhibitory effect of DOC on fluid and sodium absorption is 2 mmol. In order to decrease PD and increase the colonic permeability for 14C-erythritol the same concentration was needed.2.In contrast, DOC stimulated potassium and mucus secretion even in a fourfold lower concentration (0.5 mmol). No difference in the responsiveness of the descending and ascending colon was observed.3.It is concluded that the identical dose dependency of the effect of DOC on fluid and sodium movement, PD, and permeability of the colonic mucosa is consistent with the interpretation that the secretagogue effect of DOC is mediated by an increase in permeability. However, because of their greater sensitivity, mucus and potassium secretion obviously are affected by a different mechanism. It is speculated that mucus and potassium are secreted together by the mucus producing cells of the colonic mucosa under the influence of DOC.

The influence of water gradients and oxyphenisatin on the net transfer of sodium and water in the rat colon

Summary1.The net transfer of sodium, chloride and fluid was investigated in rat colon under the influence of oxyphenisatin, after filling tied off segments with choline chloride or sodium sulfate solutions of different osmotic pressure.2.The colonic mucosa behaves like a semipermeable membrane. In spite of the steep concentration gradient which results after filling the segments with solutions without sodium or chloride there is no net transfer of sodium and chloride from blood to lumen.3.Oxyphenisatin abolishes the ability of the colonic mucosa to maintain a steep concentration gradient for sodium and chloride from blood to lumen. Consequently, sodium, chloride and water flow into the lumen.4.Under the influence of oxyphenisatin water movement across the intestinal wall induced by osmotic gradients does not affect the net transfer of sodium from blood to lumen. This indicates that under these conditions sodium and water moving into the lumen take different pathways through the epithelium.

Influx and efflux of sodium in jejunal and colonic segments of rats under the influence of oxyphenisatin.

Summary1.The influence of oxyphenisatin on the unidirectional fluxes of sodium in the jejunum and the colon of the rat was measured in vivo by means of 22Na and 24Na.2.In the jejunum, the ratio