Taurodeoxycholate and the developing rabbit distal colon: absence of secretory effect

1987 ◽  
Vol 253 (4) ◽  
pp. G483-G488 ◽  
Author(s):  
G. D. Potter ◽  
R. Lester ◽  
S. M. Burlingame ◽  
P. A. Mitchell ◽  
K. L. Schmidt

Failure to absorb bile acids by the ileum leads to fluid secretion by the colon and diarrhea in adults. The infant ileum, however, does not actively transport bile acids. Therefore, we investigated the effect of taurodeoxycholic acid (TDCA) on ion transport in the colon of rabbits 7-10 days old. We mounted distal colon from infant and adult rabbits in modified Ussing chambers and exposed the mucosal or serosal surfaces to TDCA. In the adult, 50 microM TDCA produced an increase in short-circuit current (delta Isc = 1.0 +/- 0.3 mu eq . h-1 . cm-2, P less than 0.05) and Cl secretion. In the infant, the effect was different, Isc was reduced (delta Isc = -1.1 +/- 0.2 mu eq . h-1 . cm-2, P less than 0.01) and ion flux was not altered. Microscopy demonstrated that the infant epithelium was not significantly damaged by exposure to TDCA at these concentrations. The infant colon was, however, capable of a secretory response to a variety of agonists including theophylline, carbachol, bradykinin, serotonin, and 12,13-dibutyryl phorbol ester. The infant rabbit distal colon lacks a secretory response to TDCA during that period when the ileum cannot transport bile acids.

1995 ◽  
Vol 269 (2) ◽  
pp. R426-R431 ◽  
Author(s):  
T. R. Traynor ◽  
D. R. Brown ◽  
S. M. O'Grady

Electrical transmural stimulation (ETS) was used to examine the neuroregulation of electrolyte transport in the porcine distal colon. ETS of the colonic mucosa-submucosa mounted in Ussing chambers produced rapid and transient increases in short-circuit current (Isc) that were inhibited 36% by serosal bumetanide, suggesting that a portion of the response may be attributed to Cl secretion. ETS actions were dependent upon stimulus intensity and frequency and were inhibited by tetrodotoxin and omega-conotoxin. Prazosin and pyrilamine had no effect on the mucosal responses to ETS, whereas atropine reduced the responses by 32%. Neuropeptide Y (NPY) also reduced the mucosal responses to ETS up to 60% (half-maximal effective concentration = 17 nM). In addition, the effects of leukotriene C4, previously shown to stimulate Cl secretion via a neuronal pathway, were also inhibited by NPY. These results indicate that cholinergic submucosal neurons play a role in the regulation of epithelial ion transport and that NPY acts as an inhibitory neuromodulator, particularly on leukotriene-sensitive neurons in the porcine distal colon.


1986 ◽  
Vol 61 (3) ◽  
pp. 1065-1070 ◽  
Author(s):  
R. J. Corrales ◽  
D. L. Coleman ◽  
D. B. Jacoby ◽  
G. D. Leikauf ◽  
H. L. Hahn ◽  
...  

Sheets of trachea from ferret and cat were mounted in Ussing chambers and continuously short circuited. Under resting conditions, in both the cat and ferret there was little or no Cl secretion, and Na absorption accounted for most of the short-circuit current (Isc). Ouabain (10(-4) M, serosal bath) reduced Isc to zero in 30–60 min. This decline was matched by a decrease in net Na absorption. Amiloride (10(-4) M, luminal bath) caused a significant decrease in Isc and conductance (G) in both species. Bumetanide (10(-4) M, serosal bath) had negligible effects on Isc and G. In both species, isoproterenol increased Isc by stimulating Cl secretion. Methacholine induced equal amounts of Na and Cl secretion, with little change in Isc. In the cat, prostaglandins E2 and F2 alpha and bradykinin increased Isc, responses which were abolished in Cl-free medium. In open-circuited cat tissues, Na flux from the serosal to mucosal side was measured simultaneously with the secretion of nondialyzable 35S. Prostaglandins E1, E2, and F2 alpha, histamine, bradykinin, methacholine and isoproterenol all increased both Na and 35S-mucin secretion.


1991 ◽  
Vol 260 (4) ◽  
pp. C750-C755 ◽  
Author(s):  
T. R. Traynor ◽  
S. M. O'Grady

Porcine distal colon epithelium was mounted in Ussing chambers and bathed with porcine Ringer solution. The serosal addition of brain natriuretic peptide (BNP; 50 nM) or atriopeptin III (AP-III; 500 nM) produced significant increases (50-75 microA/cm2) in short-circuit current (Isc). These increases in Isc were not inhibited by pretreatment with tetrodotoxin (TTX) or 5,8,11,14-eicosatetraynoic acid (ETYA). Analysis of concentration-response relationships revealed that BNP was 5.8-fold more potent than AP-III in stimulating the Isc. BNP and AP-III significantly increased the serosal-to-mucosal (S----M) Cl flux and reduced net Cl absorption by 38 and 41%, respectively. The BNP-stimulated S----M Cl flux was abolished when HCO3 was removed. In contrast, the vasoactive intestinal peptide (VIP)-stimulated S----M Cl flux was not affected by HCO3 replacement. In addition to their effects on Cl transport, BNP and AP-III increased net Rb secretion by 79 and 58%, respectively. BNP-stimulated Rb secretion was reduced by 76% after HCO3 replacement. These results indicate that natriuretic peptides stimulate K- and HCO3-dependent Cl secretion which is not present under basal conditions or after VIP stimulation. The difference in potency between BNP and AP-III suggests that ANP-B receptors may mediate their effects on ion transport in the porcine colon.


1990 ◽  
Vol 259 (1) ◽  
pp. G62-G69 ◽  
Author(s):  
L. L. Clarke ◽  
R. A. Argenzio

In contrast to in vivo findings, the equine proximal colon fails to demonstrate significant net absorption of Na+ and Cl- under in vitro conditions. The present study was undertaken to determine if endogenous prostanoids are responsible for this apparent lack of ion transport. Proximal colonic tissues from ponies were preincubated in either normal Ringer solution or in Ringer containing 1 microM indomethacin and studied in Ussing chambers containing these solutions. Untreated colonic mucosa demonstrated negligible Na(+)-Cl- absorption in the basal state. In contrast, indomethacin-treated colon significantly absorbed Na+ and Cl-, primarily as the result of an equivalent increase in the mucosal-to-serosal flux of these ions. Preincubation of proximal colon in 0.1 mM ibuprofen-treated Ringer yielded similar results. Treatment of indomethacin colon with 1 mM mucosal amiloride eliminated net Na(+)-Cl- absorption without affecting the short-circuit current (Isc). The Isc in control tissue was significantly greater than in indomethacin-treated tissue and was reduced by 0.1 mM serosal furosemide. Serosal addition of 0.1 microM prostaglandin E2 or 10 mM serosal plus mucosal theophylline to indomethacin-treated tissues abolished net Na(+)-Cl- absorption and increased the Isc to levels indistinguishable from control. In contrast, control tissues were essentially unaffected by these secretagogues. These findings indicated that Na(+)-Cl- absorption in equine proximal colon was electroneutral (possibly involving Na(+)-H+ exchange) and that the tissue was capable of electrogenic Cl- secretion. However, under the in vitro conditions, basal ion transport was dominated by endogenous prostanoids that abolished Na(+)-Cl- absorption and elicited near-maximal electrogenic Cl- secretion.


2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P107-P107
Author(s):  
Do-Yeon Cho ◽  
Illek Beate ◽  
Fischer Horst ◽  
Peter H Hwang

Problem Epithelial ion transport regulates hydration of respiratory mucosal surfaces, which promotes effective mucociliary clearance. Activators of chloride ion (Cl-) secretion, such as ascorbic acid (Vitamin C), may enhance the rheologic properties of mucus. Altered ion transport could play a role in the pathogenesis of chronic rhinosinusitis (CRS). The purpose of this study is to assess the electrophysiologic characteristics and role of vitamin C on the nasal mucosa of CRS patients. Methods Nasal tissues (uncinate process, inferior turbinate, nasal septum) were obtained from five CRS patients during sinus surgery and mounted on disks with open areas of 0.03cm2 to 0.71cm2 between Ussing hemichambers. Short-circuit current (Isc) was continuously recorded, and at 50-s intervals transepithelial voltage was clamped from 0 to 2mV. Serosa-to-mucosa-directed Cl- gradient was applied to increase the electrochemical driving force for Cl- exit across the apical membrane. Results Isc decreased when the epithelial Na+ channel blocker (amiloride) was added to the luminal side of the chamber indicating that the tissues were Na+ absorbing. Addition of the cAMP-elevating agonist forskolin induced a Cl- secretory response and exposure of the apical airway surface to vitamin C(600uM) stimulated the transepithelial Cl- secretion to 60% of the forskolin-stimulated Isc. The contribution of the Na+/K+/2Cl- cotransporter to the Cl- secretory response was verified by addition of bumetamide. Glybenclamide was used to probe for the CFTR-Cl- conductance. These results were observed in all specimens. Conclusion Freshly excised human nasal epithelium is easily accessible and its bioelectric measurements can be applied as a functional measurement of ion transport in epithelial diseases. Vitamin C may serve as a biological regulator of CFTR-mediated Cl- secretion in human nasal epithelia. Significance Vitamin C in human nasal epithelia may represent a potential target for the complementary treatment of thickened mucus secretions by enhancing epithelial fluid secretion in diseases, such as CRS or cystic fibrosis.


1989 ◽  
Vol 256 (4) ◽  
pp. G721-G726 ◽  
Author(s):  
Y. H. Tai ◽  
T. P. Gage ◽  
C. McQueen ◽  
S. B. Formal ◽  
E. C. Boedeker

To investigate the characteristics of intestinal ion and fluid secretion induced by the adherent, effacing enteropathogenic Escherichia coli strain RDEC-1, we infected weanling rabbits with 10(7)-10(8) RDEC-1 organisms and then studied cecal ion transport under short-circuit conditions in Ussing chambers. Results in tissues with confluent adherent organisms were compared with those in uninfected ceca and in ceca stimulated with dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). The short-circuited cecum normally absorbed Na and Cl, secreted bicarbonate (as represented by the residual ion flux), and displayed a high rate of nondiffusional Na and Cl transport. RDEC-1 infection did not alter the short-circuit current (Isc), but it increased the conductance (Gt), decreased the potential difference (PD), abolished net Na absorption, and reversed Cl absorption to secretion. The changes in Na and Cl net fluxes may be explained by inhibition of a Na-Cl linked absorptive process. In contrast, DBcAMP significantly increased the Isc, PD, and Gt, decreased net Na flux, and abolished net Cl absorption by stimulating electrogenic Cl secretion. These results suggest that RDEC-1-induced changes in cecal ion transport are not mediated by cAMP. The reduction in Na-Cl linked absorption is consistent with anatomic changes in the apical surfaces of absorptive epithelial characteristic of effacing enteroadherence, whereas the increased conductance is consistent with tight junction disruption seen with RDEC-1 infection.


1993 ◽  
Vol 264 (5) ◽  
pp. G848-G854 ◽  
Author(s):  
G. H. Ballantyne ◽  
J. R. Goldenring ◽  
F. X. Fleming ◽  
S. Rush ◽  
J. S. Flint ◽  
...  

Neurocrine, endocrine, and paracrine regulators are critical to the control of colonic secretion. These studies have investigated the inhibition of vasoactive intestinal polypeptide (VIP)-stimulated ion transport by peptide YY (PYY) and other Y-class effectors in rabbit distal colonic mucosa mounted in Ussing chambers. PYY decreased basal short-circuit current (Isc) but did not significantly change either basal Na+ or Cl- flux. PYY inhibited VIP-stimulated increases in Isc by up to 86% and abolished VIP-induced Cl- secretion. PYY decreased VIP-generated increases in Isc by a tetrodotoxin-insensitive mechanism. PYY inhibited cholera toxin-stimulated as well as forskolin-stimulated increases in Isc but failed to alter stimulation by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). PYY decreased VIP-stimulated increases in tissue cAMP by 88% and forskolin-stimulated increases by 84%. PYY, neuropeptide Y (NPY), (Leu31,Pro34)-NPY, and pancreatic polypeptide (PP) all demonstrated potent inhibition of VIP-stimulated increases in Isc. PYY-(13-36) demonstrated little effect on VIP stimulation. Thus the rabbit distal colon possesses a novel Y-class receptor phenotype that demonstrates high affinity for all three PP-fold peptides, NPY, PYY, and PP.


1992 ◽  
Vol 82 (6) ◽  
pp. 673-680 ◽  
Author(s):  
S. P. L. Travis ◽  
D. P. Jewell

1. Platelet-activating factor is an inflammatory mediator related to eicosanoids which is known to stimulate anion secretion in the distal colon. Since there are regional differences in ion transport within the colon, the influence of platelet-activating factors on ion transport and epithelial permeability has been studied in rabbit caecum and distal colon mounted in Ussing chambers. 2. The effect of platelet-activating factor (1–50 nmol/l) on net electrogenic ion transport was to stimulate a biphasic increase in short-circuit current in the distal colon but not in the caecum. The platelet-activating factor-induced rise in short-circuit current was shown by ion replacement and pharmacological inhibitor studies to be consistent with chloride and bicarbonate secretion in the early phase, but with chloride secretion alone in the later phase. The effect on ion transport was specific and reversible and was enhanced by 0.25% BSA. 3. Colonic permeability, assessed by transmucosal resistance and mannitol flux, was increased by platelet-activating factor in both the distal colon and the caecum. This was consistent with an effect on platelet-activating factor on the paracellular pathway, because resistance decreased even when transcellular chloride transport was inhibited by frusemide or ion replacement. A specific platelet-activating factor antagonist (U66985) inhibited the effects of platelet-activating factor in both the distal colon and the caecum. 4. The results show that platelet-activating factor stimulates anion secretion only in the distal colon, but increases permeability in both the caecum and the distal colon.


1994 ◽  
Vol 267 (1) ◽  
pp. R156-R163 ◽  
Author(s):  
H. V. Carey ◽  
U. L. Hayden ◽  
K. E. Tucker

Three-week-old piglets were used to study the effects of short-term fasting on jejunal ion transport. A 48-h fast significantly reduced mucosal weight, villus height, and crypt depth. Fasting increased basal short-circuit current (Isc), which reflects active ion transport, and total tissue conductance (Gt) of muscle-stripped jejunal sheets mounted in Ussing chambers. Increases in Isc evoked by carbachol, serotonin, histamine, prostaglandin E2, or Escherichia coli heat-stable enterotoxin were significantly greater in the fasted piglets. Isc responses to mucosal D-glucose were also enhanced by the fast. Under basal conditions, unidirectional and net fluxes of Na+ and Cl-, as well as serosal-to-mucosal inulin fluxes, were significantly increased in fasted piglets. In fed piglets, carbachol increased net Cl- secretion by stimulating serosal-to-mucosal Cl- flux; Gt was not affected. In fasted piglets, carbachol increased net Cl- secretion by inhibiting mucosal-to-serosal fluxes with no effect on serosal-to-mucosal fluxes. In addition, carbachol significantly inhibited mucosal-to-serosal Na+ fluxes and reduced Gt in this group. Thus a 48-h fast increased unidirectional and net ion fluxes in piglet jejunum and enhanced ion transport responses to secretory agonists. The mechanism by which carbachol stimulated net Cl- secretion was also altered by the fast. These results suggest that the absence of luminal nutrition changes the ion transport characteristics of the jejunal epithelium.


1994 ◽  
Vol 267 (4) ◽  
pp. R1026-R1033 ◽  
Author(s):  
M. D. DuVall ◽  
S. M. O'Grady

Intact epithelium from the porcine distal colon was stripped of serosal muscle and mounted in Ussing chambers to investigate the regulation of Na, Cl, and K transport by guanosine 3',5'-cyclic monophosphate (cGMP) and elevations in intracellular [Ca2+]. Under voltage-clamped conditions cGMP (250 microM) produced an increase in tissue short-circuit current (Isc) that reached a maximal value within 10-20 min and remained elevated > 40 min. This response was associated with an inhibition of NaCl absorption and stimulation of Cl and K secretion. In the absence of Cl the Isc also slowly increased but returned to baseline values within 20 min. Bicarbonate removal from both serosal and mucosal solutions or serosal bumetanide (20 microM) reduced the effect of cGMP on Isc by approximately 40%. When performed simultaneously, these conditions reduced the cGMP response by approximately 60%. Transepithelial Na and Cl flux measurements indicated that serosal bumetanide blocked increased Cl secretion without effecting changes in NaCl absorption. In contrast, mucosal amiloride blocked the effects of cGMP on NaCl absorption but not Cl secretion. The cGMP Isc response was potentiated in the presence of 1 mM, but not 10 microM, amiloride. Moreover, 1 mM amiloride inhibited Isc under control conditions but was ineffective in the presence of cGMP. The Ca2+ ionophore ionomycin (3 microM) produced a transient increase in the Isc that was also associated with a decrease in transepithelial NaCl absorption and an increase in Cl and K secretion. In contrast to cGMP, the ionomycin Isc response was eliminated after Cl removal from the bath.(ABSTRACT TRUNCATED AT 250 WORDS)


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