scholarly journals Regulation of electrolyte transport with IL-1β in rabbit distal colon

1995 ◽  
Vol 4 (1) ◽  
pp. 61-66 ◽  
Author(s):  
F. R. Homaidan ◽  
H. Desai ◽  
L. Zhao ◽  
G. Broutman ◽  
R. Burakoff
Keyword(s):  
Inflammatory Bowel Disease ◽  
Protein Synthesis ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Electrolyte Transport ◽  
Interleukin 1Β ◽  
Prostaglandin E ◽  
Inflammatory Bowel

Interletrkin-1β levels are elevated in inflammatory bowel disease. In this study the mechanism by which interleukin-1β affects electrolyte transport in the rabbit distal colon, was investigated. Interleukin-1β caused a delayed increase in short-circuit current (Isc) which was attributed to protein synthesis since the effect was inhibited by cycloheximide. The interleukin-1β induced increase in Iscwas not affected by amiloride treatment but was completely inhibited by bumetanide or in chloride-free buffer and by indomethacin. Prostaglandin E2levels increased in tissue treated with interleukin-1β, but this increase was reversed by cycloheximide. These data suggest that interleukin-1β causes its effect via a yet to be identified second messenger, by increasing chloride secretion through a prostaglandin E2mediated mechanism.

Corticosteroid alteration of active electrolyte transport in rat distal colon

1983 ◽  
Vol 245 (5) ◽  
pp. G668-G675 ◽  
Author(s):  
E. S. Foster ◽  
T. W. Zimmerman ◽  
J. P. Hayslett ◽  
H. J. Binder
Keyword(s):  
Colonic Mucosa ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Transport Processes ◽  
Electrolyte Transport ◽  
Sodium Absorption ◽  
Rat Distal Colon ◽  
Potassium Absorption ◽  
Potassium Secretion

To determine the effect of corticosteroids on active transport processes, unidirectional fluxes of 22Na, 36Cl, and 42K were measured under short-circuit conditions across isolated stripped distal colonic mucosa of the rat in control, secondary hyperaldosterone, and dexamethasone-treated animals. In controls net sodium and chloride fluxes (JNanet and JClnet) and short-circuit current (Isc) were 6.6 +/- 2.2, 7.6 +/- 1.6, and 1.3 +/- 0.2 mu eq X h-1 X cm-2, respectively. Although aldosterone increased Isc to 7.3 +/- 0.5 mu eq X h-1 X cm-2, JNanet (6.9 +/- 0.7 mu eq X h-1 X cm-2) was not altered and JClnet was reduced to 0 compared with controls. Dexamethasone also stimulated Isc but did not inhibit JClnet. In Cl-free Ringer both aldosterone and dexamethasone produced significant and equal increases in JNanet and Isc. Theophylline abolished JNanet in control animals but not in the aldosterone group. Aldosterone reversed net potassium absorption (0.58 +/- 0.11 mu eq X h-1 X cm-2) to net potassium secretion (-0.94 +/- 0.08 mu eq X h-1 X cm-2). Dexamethasone reduced net potassium movement to 0 (-0.04 +/- 0.12 mu eq X h-1 X cm-2). These studies demonstrate that 1) corticosteroids stimulate electrogenic sodium absorption and 2) aldosterone, but not dexamethasone, inhibits neutral NaCl absorption and stimulates active potassium secretion. The effects of mineralocorticoids and glucocorticoids on electrolyte transport are not identical and may be mediated by separate and distinct mechanisms.

Role of calcium in chloride secretion mediated by cAMP pathway activation in rabbit distal colon mucosa

1993 ◽  
Vol 264 (2) ◽  
pp. G252-G260 ◽  
Author(s):  
V. Calderaro ◽  
E. Chiosi ◽  
R. Greco ◽  
A. M. Spina ◽  
A. Giovane ◽  
...  
Keyword(s):  
Short Circuit ◽  
Fold Increase ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Free Medium ◽  
Cl Secretion ◽  
Pathway Activation ◽  
Flux Measurements ◽  
Pg E2

Effects of Ca2+ on adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- secretion were investigated in intact mucosa and isolated crypt cells of rabbit descending colon. Addition of 10 microM prostaglandin (PG)E2 or forskolin to tissues incubated in Ca(2+)-free medium increased the size of short-circuit current (Isc) and Cl- secretion as estimated by unidirectional 36Cl flux measurements (net flux = -2.31 +/- 0.24 vs. -1.22 +/- 0.10 mueq.h-1.cm-2, n = 4, P < 0.001). Addition of 10 microM PGE2 to tissues incubated in 1.2 mM Ca2+ Ringer induced a 7-fold increase in mean cAMP level, whereas it produced an 11-fold increase in tissues exposed to Ca(2+)-free medium. Membrane preparations from whole mucosa incubated in Ca(2+)-free medium displayed a cyclic nucleotide phosphodiesterase activity significantly lower than controls (18.76 +/- 0.54 vs. 31.20 +/- 0.39 pmol cAMP. mg protein-1.min-1, means +/- SE, n = 4, P < 0.001). Ca2+ removal also affected adenylate cyclase (AC) responsiveness to agonists; AC activity increased in controls by 54 and 226% after stimulation with 10 microM PGE2 and forskolin, respectively, but it increased more (77 and 325%, respectively) after incubation in Ca(2+)-free solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

cAMP-dependent sulfate secretion by the rabbit distal colon: a comparison with electrogenic chloride secretion

1997 ◽  
Vol 273 (1) ◽  
pp. C148-C160 ◽  
Author(s):  
R. W. Freel ◽  
M. Hatch ◽  
N. D. Vaziri
Keyword(s):  
Short Circuit ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Disulfonic Acid ◽  
Cl Secretion ◽  
Cyclic Monophosphate ◽  
Anion Conductance ◽  
Flux Measurements

The ability of a Cl-secreting epithelium to support net secretion of an anion other than a halide was investigated with 35SO4 flux measurements across the isolated, short-circuited rabbit distal colon. In most experiments, 36Cl fluxes were simultaneously measured to validate the secretory capacity of the tissues. Serosal addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, 0.5 mM) stimulated a sustained net secretion of SO4 (about -3.0 nmol.cm-2.h-1 from a 0.20 mM solution) via an increase in the serosal-to-mucosal unidirectional flux, whereas Ca ionophore A-23187 (1 microM, serosal) produced a more transient stimulation of SO4 and Cl secretion. Net adenosine 3',5'-cyclic monophosphate (cAMP)-dependent SO4 and Cl secretion were strongly voltage sensitive, principally through the potential dependence of the serosal-to-mucosal fluxes, indicating an electrogenic transport process. Symmetrical replacement of either Na, K, or Cl inhibited cAMP-dependent SO4 secretion, whereas HCO3-free buffers had no effect on SO4 secretion. Serosal bumetanide (50 microM) or furosemide (100 microM) reduced DBcAMP-stimulated SO4 and Cl secretion, whereas serosal 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid or 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (50 microM) blocked DBcAMP-induced SO4 secretion while enhancing net Cl secretion and short-circuit current. Mucosal 5-nitro-2-(3-phenylpropylamino)benzoic acid partially inhibited SO4 secretion and completely inhibited Cl secretion. It is concluded that secretagogue-stimulated SO4 secretion, like Cl secretion, may be an electrogenic process mediated by diffusive efflux through an apical anion conductance. Cellular accumulation of SO4 across the basolateral membrane appears to be achieved by a mechanism that is distinct from that employed by Cl.

Substance P as a mediator of colonic secretory reflexes

1997 ◽  
Vol 272 (2) ◽  
pp. G238-G245 ◽  
Author(s):  
H. J. Cooke ◽  
M. Sidhu ◽  
P. Fox ◽  
Y. Z. Wang ◽  
E. M. Zimmermann
Keyword(s):  
Substance P ◽  
Messenger Rna ◽  
Short Circuit ◽  
Chronic Administration ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Intestinal Epithelial ◽  
Axon Reflex ◽  
Reflex Pathways

The role of substance P in neural reflex pathways activated by stroking was investigated in muscle-stripped segments of distal colon from guinea pigs. Stroking the mucosal surface with a brush at 1 stroke/s evoked an increase in short-circuit current (Isc) indicative of chloride secretion. The response to mucosal stroking was maximally reduced by 69-75% by the antagonist GR-82334. The agonist [Sar9,Met(O2)11] substance P caused a bumetanide-sensitive increase in Isc when added to the mucosal or serosal bath. Ablation of extrinsic afferents with acute or chronic administration of capsaicin did not alter the mucosal stroking response. Reverse transcription-polymerase chain reaction and in situ hybridization revealed the presence of neurokinin1 (NK1) receptor messenger RNA in isolated colonocytes or crypt glands. Ligand binding of 125I-Bolton-Hunter-labeled substance P was inhibited by GR-82334. The 50% inhibitory concentration was 0.84 nM. The results demonstrate a role for substance P released from capsaicin-insensitive submucosal neurons and in mucosal stroking reflexes. The presence of NK1 receptors on isolated colonocytes suggests that appropriate elements are present for axon reflex activation of intestinal epithelial cells.

5-HT activates nitric oxide-generating neurons to stimulate chloride secretion in guinea pig distal colon

1998 ◽  
Vol 275 (4) ◽  
pp. G829-G834 ◽  
Author(s):  
Atsukazu Kuwahara ◽  
Hirofumi Kuramoto ◽  
Makoto Kadowaki
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Evoked Response ◽  
Evoked Responses ◽  
No Donor ◽  
Simultaneous Application

The participation of nitric oxide (NO) in serotonin (5-hydroxytryptamine; 5-HT)-evoked chloride secretion in guinea pig distal colon was examined. Submucosal/mucosal segments were mounted in Ussing flux chambers, and an increase in short-circuit current ( I sc) was used as an index of secretion. Addition of 5-HT to the serosal side produced a concentration-dependent (10−7–10−5M) increase in I sc caused by chloride secretion. N G-nitro-l-arginine (l-NNA) significantly reduced the 5-HT-evoked early (P-1) and late (P-2) responses to 61.1 and 70.6% of control, respectively. Neurally evoked response was also inhibited by l-NNA. The NO donor sodium nitroprusside (SNP, 10−4 M) increased basal I sc mainly because of chloride secretion. The SNP-evoked response was significantly reduced by tetrodotoxin but was unchanged by atropine or indomethacin. These results suggest that the 5-HT-evoked increase in I sc is associated with an NO-generating mechanism. Atropine significantly reduced the 5-HT (10−5 M)-evoked P-1 and P-2 responses to 71.8 and 19.7% of control, respectively. Simultaneous application of atropine andl-NNA further decreased the 5-HT-evoked responses more than either drug alone; application ofl-NNA and atropine decreased the 5-HT-evoked P-1 and P-2 responses to 68.5 and 39.2% of atropine-treated tissues, respectively. These results suggest that noncholinergic components of P-1 and P-2 responses are 71.8 and 19.7% of control, respectively, and that NO components of P-1 and P-2 responses are 32 and 61%, respectively, of the noncholinergic component of the 5-HT-evoked responses. The results provide evidence that NO may participate as a noncholinergic mediator of 5-HT-evoked chloride secretion in guinea pig distal colon.

scholarly journals Prostaglandin E2 mediates proliferation and chloride secretion in ADPKD cystic renal epithelia

2012 ◽  
Vol 303 (10) ◽  
pp. F1425-F1434 ◽  
Author(s):  
Yu Liu ◽  
Madhumitha Rajagopal ◽  
Kim Lee ◽  
Lorenzo Battini ◽  
Daniel Flores ◽  
...  
Keyword(s):  
Short Circuit ◽  
Ussing Chamber ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Cell Number ◽  
Flufenamic Acid ◽  
Prostaglandin E ◽  
Intracellular Camp ◽  
Ep4 Receptor ◽  
Autosomal Dominant Polycystic Kidney

Prostaglandin E2 (PGE2) contributes to cystogenesis in genetically nonorthologous models of autosomal dominant polycystic kidney disease (ADPKD). However, it remains unknown whether PGE2 induces the classic features of cystic epithelia in genetically orthologous models of ADPKD. We hypothesized that, in ADPKD epithelia, PGE2 induces proliferation and chloride (Cl−) secretion, two archetypal phenotypic features of ADPKD. To test this hypothesis, proliferation and Cl− secretion were measured in renal epithelial cells deficient in polycystin-1 (PC-1). PC-1-deficient cells increased in cell number (proliferated) faster than PC-1-replete cells, and this proliferative advantage was abrogated by cyclooxygenase inhibition, indicating a role for PGE2 in cell proliferation. Exogenous administration of PGE2 increased proliferation of PC-1-deficient cells by 38.8 ± 5.2% ( P < 0.05) but inhibited the growth of PC-1-replete control cells by 49.4 ± 1.9% ( P < 0.05). Next, we tested whether PGE2-specific E prostanoid (EP) receptor agonists induce intracellular cAMP and downstream β-catenin activation. PGE2 and EP4 receptor agonism (TCS 2510) increased intracellular cAMP concentration and the abundance of active β-catenin in PC-1-deficient cells, suggesting a mechanism for PGE2-mediated proliferation. Consistent with this hypothesis, antagonizing EP4 receptors reverted the growth advantage of PC-1-deficient cells, implicating a central role for the EP4 receptor in proliferation. To test whether PGE2-dependent Cl− secretion is also enhanced in PC-1-deficient cells, we used an Ussing chamber to measure short-circuit current ( Isc). Addition of PGE2 induced a fivefold higher increase in Isc in PC-1-deficient cells compared with PC-1-replete cells. This PGE2-induced increase in Isc in PC-1-deficient cells was blocked by CFTR-172 and flufenamic acid, indicating that PGE2 activates CFTR and calcium-activated Cl− channels. In conclusion, PGE2 activates aberrant signaling pathways in PC-1-deficient epithelia that contribute to the proliferative and secretory phenotype characteristic of ADPKD and suggests a therapeutic role for PGE2 inhibition and EP4 receptor antagonism.

scholarly journals The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO3− by the Porcine Colon

2021 ◽  
Vol 22 (10) ◽  
pp. 5198
Author(s):  
David Manneck ◽  
Gisela Manz ◽  
Hannah-Sophie Braun ◽  
Julia Rosendahl ◽  
Friederike Stumpff
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gastrointestinal Tract ◽  
Patch Clamp ◽  
Bowel Disease ◽  
Colonic Mucosa ◽  
Therapeutic Potential ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Ussing Chambers ◽  
Inflammatory Bowel

A therapeutic potential of the TRPA1 channel agonist cinnamaldehyde for use in inflammatory bowel disease is emerging, but the mechanisms are unclear. Semi-quantitative qPCR of various parts of the porcine gastrointestinal tract showed that mRNA for TRPA1 was highest in the colonic mucosa. In Ussing chambers, 1 mmol·l−1 cinnamaldehyde induced increases in short circuit current (ΔIsc) and conductance (ΔGt) across the colon that were higher than those across the jejunum or after 1 mmol·l−1 thymol. Lidocaine, amiloride or bumetanide did not change the response. The application of 1 mmol·l−1 quinidine or the bilateral replacement of 120 Na+, 120 Cl− or 25 HCO3− reduced ΔGt, while the removal of Ca2+ enhanced ΔGt with ΔIsc numerically higher. ΔIsc decreased after 0.5 NPPB, 0.01 indometacin and the bilateral replacement of 120 Na+ or 25 HCO3−. The removal of 120 Cl− had no effect. Cinnamaldehyde also activates TRPV3, but comparative measurements involving patch clamp experiments on overexpressing cells demonstrated that much higher concentrations are required. We suggest that cinnamaldehyde stimulates the secretion of HCO3− via apical CFTR and basolateral Na+-HCO3− cotransport, preventing acidosis and damage to the epithelium and the colonic microbiome. Signaling may involve the opening of TRPA1, depolarization of the epithelium and a rise in PGE2 following a lower uptake of prostaglandins via OATP2A1.

Effects of tetrodotoxin on chloride secretion in rabbit distal colon: tissue and cellular studies

1990 ◽  
Vol 258 (2) ◽  
pp. G223-G230 ◽  
Author(s):  
B. Biagi ◽  
Y. Z. Wang ◽  
H. J. Cooke
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Resting Potential ◽  
Colon Tissue ◽  
Colonic Crypts ◽  
Electrophysiological Studies ◽  
Release Of Acetylcholine

The effects of tetrodotoxin (TTX) were examined in muscle-stripped segments of rabbit distal colon and in cells of isolated colonic crypts. Electrical field stimulation (EFS) of the submucosa/mucosa evoked an increase in short-circuit current (ISC) that was due to an increase in chloride secretion. The EFS-evoked response was reduced 81% by 10(-7) M TTX and 30% by 5 X 10(-6) M atropine. Vasoactive intestinal peptide (VIP), carbachol, aminophylline, and 1,1-dimethyl-4-phenylpiperazinium increased ISC. Bumeta nide reduced the responses to neural stimulation, aminophylline, and VIP. To determine whether TTX had direct effects on crypt epithelial cells, crypts were isolated and cells were impaled with microelectrodes. Mean resting potential (Vbl) was -67 +/- 1.1 mV (n = 63). VIP and aminophylline depolarized Vbl by 34 +/- 4.6 (n = 13) and 34 +/- 3.5 mV (n = 18), respectively. TTX had no significant effect on resting Vbl or on the responses to VIP or aminophylline. We conclude that stimulation of submucosal neurons in the rabbit distal colon evokes a TTX- and bumetanide-sensitive increase in net chloride secretion that is dependent on the release of acetylcholine and other secretory neurotransmitters. Electrophysiological studies rule out a direct effect of TTX on colonic crypt cells.

H2 receptors mediate cyclical chloride secretion in guinea pig distal colon

1990 ◽  
Vol 258 (6) ◽  
pp. G887-G893 ◽  
Author(s):  
Y. Z. Wang ◽  
H. J. Cooke
Keyword(s):  
Guinea Pig ◽  
Chloride Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Chloride Ions ◽  
H2 Antagonist ◽  
H2 Receptors ◽  
Peak Increase

We tested the hypothesis that histamine mediates ion secretion in the guinea pig distal colon by stimulating H2 receptors on submucosal neurons. Serosal addition of histamine evoked a transient increase in short-circuit current (Isc) followed by recurrent cyclical increases in Isc. The transient phase of the response was examined previously and was not investigated in these studies. Histamine (1.5-2.5 x 10(-5) M) evoked a peak increase in Isc of 177 +/- 25 microA/cm2 at intervals of 5 min for 1-2 h. The duration of each recurrent cycle averaged 2.1 +/- 0.3 min. The H2 agonist dimaprit evoked recurrent cycles that had larger amplitudes than those caused by histamine. In the presence of histamine or dimaprit, the amplitude of the first cycle of the response was always less than subsequent cycles, regardless of the initial concentration. The cyclical responses to histamine, 2-methylhistamine, or dimaprit were unaltered by the H1 blocker pyrilamine, were reduced by the H2 antagonist cimetidine, and were abolished by the neuronal blocker tetrodotoxin. Blockade of prostaglandin formation with piroxicam did not prevent the recurrent cycles. The recurrent cycles were inhibited by the chloride transport blocker bumetanide and by removal of chloride ions. Our results demonstrate that histamine mediates prolonged cyclical chloride secretion in the guinea pig distal colon by activating H2 receptors on submucosal neurons involved in regulation of epithelial chloride transport.

Regulation of colonic ion transport by GRP. II. GRP modulates the epithelial response to PGE2

1996 ◽  
Vol 270 (3) ◽  
pp. C859-C865 ◽  
Author(s):  
T. R. Traynor ◽  
S. M. O'Grady
Keyword(s):  
Time Course ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Electrolyte Transport ◽  
Gastrin Releasing Peptide ◽  
Transcellular Pathway ◽  
Flux Measurements ◽  
Pg E2 ◽  
Distal Colon Epithelium

The purpose of this study was to examine the potential modulatory effects of gastrin-releasing peptide (GRP) on prostaglandin (PG) E2-stimulated electrolyte transport across the distal colon epithelium. In an earlier study, PGE2 was shown to reduce net Cl absorption without altering the serosal-to-mucosal unidirectional Cl flux in porcine distal colon (19). In the present study, tissues were pretreated with serosal or mucosal GRP and subsequently stimulated with PGE2. The resulting increase in short-circuit current (ISC) was 152% (serosal GRP) and 49% (mucosal GRP) greater than control PGE2 responses alone. Serosal, but not mucosal, GRP also enhanced the ISC response to vasoactive intestinal peptide. On the basis of flux measurements, the combined effects of serosal GRP and PGE2 resulted in the activation of a transcellular pathway for Cl secretion, which was not activated by either mediator alone. The time course of the PGE2 response was also affected by GRP. Serosal GRP shortened the time to maximum ISC by 35%, whereas mucosal peptide lengthened the time to maximum ISC by 68% These results suggest that GRP acts as a modulator of PG action on electrolyte transport in the distal colon.

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