Do Thiazides Reduce Intestinal Oxalate Absorption?: A Study In Vitro Using Rabbit Colon

1994 ◽  
Vol 86 (3) ◽  
pp. 353-357 ◽  
Author(s):  
M. Hatch ◽  
N. D. Vaziri

1. The purpose of the present study was to examine the effects of various diuretics on intestinal oxalate transport. Transmural oxalate fluxes were measured across isolated, short-circuited tissue segments removed from rabbits and placed in Ussing chambers. 2. The net absorptive flux of oxalate across the distal colon was significantly reduced in the presence of trichlormethiazide at 10−4 mol/l. In contrast, this diuretic had no effect on oxalate transport in the other intestinal segments examined. Several of the thiazide diuretics tested had some inhibitory effect on colonic oxalate absorption, but at higher concentrations of 10−3 mol/l or 10−2 mol/l. 3. We conclude that the previously reported hypooxaluric effects of hydrochlorothiazide and chlorthalidone are most likely not the result of an exclusive or primary effect on intestinal oxalate transport. It is suggested that the reduction in colonic oxalate absorption that was observed with the thiazides probably involves the transport system responsible for oxalate efflux across the basolateral membrane of the colonocyte.

1994 ◽  
Vol 5 (6) ◽  
pp. 1339-1343
Author(s):  
M Hatch ◽  
R W Freel ◽  
N D Vaziri

The extrarenal elimination of oxalate via the intestine was studied in rats with chronic renal failure by measuring the magnitude and direction of oxalate fluxes across the small and large intestine. Oxalate transport was determined in vitro across short-circuited sheets of jejunum, ileum, and colon that were placed in Ussing chambers. The concentration of oxalate in plasma and urine was measured immediately before the transport studies. The results show that, 6 wk after 5/6 nephrectomy, rats with chronic renal failure have lower (decreases 50%) renal clearance of oxalate and a higher mean plasma oxalate concentration (increases 80%) than controls. The basal absorption of oxalate across the colon was changed to secretion in animals with chronic renal failure (from 12.81 +/- 2.22 (N = 9) to -14.96 +/- 2.57 (N = 11) pmol/cm2 per hour). Both the jejunum and the ileum supported a basal net secretory flux of oxalate (-19.71 +/- 2.39 (N = 13) and -30.06 +/- 2.80 (N = 16) pmol/cm2 per hour) that was unaffected by renal insufficiency. These studies demonstrate that intestinal transport systems for oxalate are altered in experimental chronic renal failure, and the distal colon is identified as the primary site for this adaptive response. In chronic renal failure, the entire intestinal tract can potentially excrete oxalate.


1993 ◽  
Vol 264 (1) ◽  
pp. G13-G21 ◽  
Author(s):  
J. H. Sellin ◽  
A. Hall ◽  
E. J. Cragoe ◽  
W. P. Dubinsky

Rabbit cecum in vitro exhibits electrogenic Na+ absorption not blocked by amiloride but inhibited by the amiloride analogue phenamil, suggesting transport mediated by modified Na+ channels in the apical membrane. To further characterize the mechanism(s) of Na+ absorption, microelectrode impalements of single epithelial cells were performed to measure intracellular potential difference (psi mc) and fractional resistance of the apical membrane, to characterize ionic conductances of the apical and basolateral membranes, and to determine the response to phenamil. The electrical potential profile of cecum (psi mc = -31 +/- 2 mV, fractional resistance = 0.71 +/- 0.03) was qualitatively similar to distal colon. The apical membrane exhibited responses suggesting both Na+ and K+ conductances, whereas the basolateral membrane appeared to have a predominant K+ conductance. Phenamil elicited a depolarization of psi mc and a decrease in fractional resistance; neither response is consistent with inhibition of an apical Na+ conductance. Studies were performed in apical membrane vesicles to characterize ionic conductances by a second independent methodology. These additional studies confirmed the presence of an apical Na+ conductance not inhibited by either amiloride or phenamil. Thus both microelectrode impalement and vesicle studies demonstrated an apical membrane Na+ conductance in rabbit cecum; this is the likely mechanism of electrogenic Na+ absorption in this epithelium. However, the anomalous response to phenamil suggests that the inhibitory effect of this agent is not directly on the conductance. The cecal transporter may be one of a family of cation channels related to, but significantly different from, the classic Na+ channel found in distal colon and other tight epithelia.


1996 ◽  
Vol 76 (1) ◽  
pp. 141-151 ◽  
Author(s):  
Gunilla Önning ◽  
Quan Wang ◽  
Björn R Weström ◽  
Nils-Georg Asp ◽  
Börje W Karlsson

The aim of the present study was to investigate whether oat saponins (avenacosides A and B) have any effect on the permeability of the rat intestine to actively and passively transported markers in vitro and in vivo. Intestinal segments were mounted in modified Ussing chambers, and thepassage of the different marker compounds from the mucosal to the serosal side was measured for 120 min. Avenacosides (1 mg/ml) gave a significantly higher passage of the macromolecule ovalbumin and there was a tendency to increased passage of [14C]D-mannitol and [15Cr]EDTA. On the other hand, the saponins did not affect the active transport of [3H]methyl glucose. When rats were given saponins (40 mg/kg body weight)together with markers by gastric intubation, the passage of [51Cr]EDTA into blood and urine was somewhat reduced. For the macromolecule bovine serum albumin, no evident effect on the passage was observed in the presence ofsaponins. Thus, in contrast to the in vitro results, the in vivo marker passage seemed to be unaffected or even reduced in the presence of avenacosides. The study shows that saponinscan affect the permeability of the rat intestine. However, this effect needs further investigation in vivo, especially regarding proteins.


2001 ◽  
Vol 29 (01) ◽  
pp. 111-118 ◽  
Author(s):  
Mohammad Alhakam Tulimat ◽  
Tadashi Ishiguchi ◽  
Susumu Kurosawa ◽  
Takashi Nakamura ◽  
Toku Takahashi

Dai-Kenchu-To (DKT) is a herbal medicine and is currently used as the treatment of paralytic ileus in Japan. We investigated the mechanism of beneficial effects of DKT in vitro. DKT-extract powder (DKT-EP; 30–300 μg/ml) caused a significant inhibition on carbachol (CCH; 10-6)-induced contraction in a concentration dependent manner of the rat distal colon. DKT-EP (100 μg/ml) consists of 20 μg/ml of Zanthoxylum Fruit, 30 μg/ml of Ginseng Root and 50 μg/ml of Ginger Rhizome. Although each of them had no effect on CCH-induced muscle contraction, the combination of three ingredients caused a significant inhibition on CCH-induced contraction.


1981 ◽  
Vol 241 (3) ◽  
pp. G215-G221
Author(s):  
M. J. Favus ◽  
M. Berelowitz ◽  
F. L. Coe

The addition of somatostatin (SRIF) to rat descending colon in vitro increased the calcium secretory flux from serosa to mucosa (Js leads to m) and reduced tissue short-circuit current (Isc) but did not alter the absorptive flux from mucosa to serosa (Js leads to m). Js leads to m increased by 37% at 10(-9) M SRIF and by 48% at 10(-6) M. The response to SRIF was not altered by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and SRIF did not interfere with stimulation of calcium Jm leads to s by 1,25(OH)2D3. Removal of sodium from the buffer abolished the stimulation of Js leads to m by SRIF without reducing basal Js leads to m. Secretory fluxes of mannitol and calcium were strongly correlated in the presence and absence of SRIF, suggesting that SRIF stimulates a paracellular transepithelial pathway for calcium. In the duodenum, SRIF altered neither calcium Js leads to m nor Isc. In the ileum, calcium Js leads to m increased and Isc decreased, as in the colon, but only by 28 and 12%, respectively. The maximal change in calcium Js leads to m caused by SRIF in these three intestinal segments was negatively correlated with the tissue concentration of immunoreactive SRIF. These results suggest that intestinal calcium secretion could, in part, be regulated by intestinal SRIF.


2001 ◽  
Vol 280 (3) ◽  
pp. F505-F512 ◽  
Author(s):  
Haikun Shi ◽  
Rivi Levy-Holzman ◽  
Francoise Cluzeaud ◽  
Nicolette Farman ◽  
Haim Garty

Corticosteroid hormone-induced factor (CHIF) is an aldosterone-induced gene, the function of which is yet unknown. It is specifically expressed in kidney collecting duct (CD) and distal colon and is upregulated by either Na+ deprivation or K+ loading. Hence, it may play a role in epithelial electrolyte transport. Previous studies have characterized regulation and tissue distribution of CHIF mRNA but provided no information on the protein itself. The present paper addresses this issue by using Western blotting, immunochemistry, and in vitro translation. CHIF is an ∼8-kDa membranal protein, and protease digestion experiments suggest that its COOH tail faces the cell interior. The protein is abundant in distal colon, kidney medulla, and papilla but cannot be detected in a variety of other tissues. Confocal immunocytochemistry demonstrates that CHIF is present in the basolateral membrane of CD principal cells and distal colon surface cells, with occasional intracellular staining. Dexamethasone and low Na+ intake increase the abundance of CHIF. Unlike previous Northern data, induction of CHIF protein by low-Na+ intake was apparent not only in the distal colon but also in the kidney.


1994 ◽  
Vol 266 (2) ◽  
pp. C552-C558 ◽  
Author(s):  
D. R. Halm ◽  
S. T. Halm

Distal colon from guinea pig was stimulated in vitro by aldosterone in Ussing chambers that allowed measurement of short-circuit current (Isc) and tissue conductance (Gt). The response to aldosterone was delayed by approximately 20 min and resulted in a negative Isc, consistent with K secretion. Approximately 1 h later the Isc began to increase and eventually became positive, consistent with subsequent stimulation of Na absorption. The Na-absorptive response could be inhibited by mucosal amiloride without altering the rate of K secretion. Similarly, K secretion could be inhibited by serosal bumetanide without altering Na absorption. In the presence of spironolactone, actinomycin D, or cycloheximide, aldosterone failed to stimulate both K secretion and Na absorption. A dose response to aldosterone provided an apparent Kd of 2.6 +/- 0.5 nM, consistent with a high-affinity receptor coupled to this secretory response. Stimulation by the K secretagogue epinephrine did not produce an additive increase in K secretion, suggesting that the same cell type responds to both aldosterone and epinephrine and that the protein induced by aldosterone was not one of the membrane proteins responsible for K secretion.


2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Hisayoshi Hayashi ◽  
Hiroki Nagai ◽  
Kou-ichiro Ohba ◽  
Manoocher Soleimani ◽  
Yuichi Suzuki

AbstractThe anion exchanger slc26a3 (DRA), which is mutated in congenital chloride-losing diarrhea, is expressed in the apical membrane of the cecum and middle-distal colon but not in the proximal colon of rodent large intestines. To elucidate the functional roles of DRA, we measured unidirectional 36Cl− and 22Na+ fluxes and HCO3− secretion in vitro in each of these segments using DRA-KO mice. Robust Cl− absorption, which was largely abolished after DRA deficiency, was present in the cecum and middle-distal colon but absent in the proximal colon. Na+ absorption was present in all three segments in both the control and DRA-KO mice. The luminal-Cl−-dependent HCO3− secretions in the cecum and middle-distal colon were abolished in the DRA-KO mice. In conclusion, DRA mediates Cl− absorption and HCO3− secretion in the mouse cecum and middle-distal colon, and may have roles in H2O absorption and luminal acid/base regulation in these segments.


1986 ◽  
Vol 250 (4) ◽  
pp. G475-G483 ◽  
Author(s):  
S. K. Sullivan ◽  
P. L. Smith

Fluxes of K from mucosa to serosa or serosa to mucosa have been examined in stripped preparations of rabbit proximal and distal colon in vitro under short-circuit conditions in Ussing chambers. Results from these studies demonstrate that steady-state radioisotopic fluxes of K are achieved after 90 min and remain constant for at least 2 h. Determination of the K concentration dependence of the serosal-to-mucosal K flux revealed that this flux contains both saturable and nonsaturable components. Addition of ouabain (0.1 mM) abolished the saturable component of the serosal-to-mucosal K flux. The mucosal-to-serosal K flux is a linear function of K concentration between 1 and 20 mM under basal conditions. In paired tissues, serosal-to-mucosal K flux is always greater than mucosal-to-serosal flux under basal conditions resulting in net K secretion. However, addition of barium (2 mM) to the mucosal or serosal bathing solution had no significant effect on either unidirectional or net K fluxes. In addition, mucosal bumetanide (0.1 mM) or removal of Cl from both bathing solutions had no significant effect on unidirectional or net K fluxes. In rabbit distal colon, Cl removal from the bathing solutions significantly reduced serosal-to-mucosal K flux, resulting in net K absorption. These results indicate that rabbit proximal colon like rabbit distal colon actively secretes K. However, unlike distal colon the proximal colon does not possess an active K uptake mechanism at the apical cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)


1985 ◽  
Vol 248 (2) ◽  
pp. G256-G259 ◽  
Author(s):  
J. F. White

The effect on HCO3- absorption of the substituted benzimidazole omeprazole, an inhibitor of active H+-K+ exchange, was examined in in vitro Amphiuma jejunum. HCO-3 absorption was measured using titration in short-circuited intestinal segments bathed in a Cl--free (SO2-(4)-based) medium (pH 7.40). At 1 mM omeprazole lowered the short-circuit current (Isc) and the absorptive flux of HCO3- from mucosa to serosa by about 40% over 1 h. When the serosal medium was maintained at pH 5.0, additions of omeprazole beginning at 0.1 mM caused proportional reductions of the Isc. Omeprazole also reduced intracellular potassium activity (aiK) from 74 to 59 mM and lowered the luminal membrane potential (psi m) slightly over 30 min when this was measured with double-barreled, K+-sensitive microelectrodes. After 30 min aiK and psi m tended to spontaneously revert toward control values. Galactose added to the mucosal medium (to 20 mM) stimulated the Isc equally in omeprazole-treated tissues and paired untreated control tissues. These results support the view that a fraction of the absorptive HCO3- flux (so-called) is driven by an active luminal exchange of H+ for K+.


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