Alterations of the VIP-stimulated cAMP pathway in rat distal colon after abdominal irradiation

2002 ◽  
Vol 282 (5) ◽  
pp. G835-G843 ◽  
Author(s):  
E. Morel ◽  
I. Dublineau ◽  
F. Lebrun ◽  
N. M. Griffiths
Keyword(s):  
Short Circuit ◽  
Major Change ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Cell Number ◽  
Rat Colon ◽  
Camp Accumulation ◽  
Ussing Chambers ◽  
Abdominal Irradiation ◽  
Vip Receptor

Ionizing radiation induces hyporesponsiveness of rat colonic mucosa to vasoactive intestinal peptide (VIP). Possible mechanisms responsible for this hyporesponsiveness of the cAMP communication pathway in rat colon were investigated. VIP- and forskolin-stimulated short-circuit current ( I sc) responses were studied after a 10-Gy abdominal irradiation in Ussing chambers as well as in single, isolated crypts. Adenylyl cyclase (AC) activity and VIP receptor characteristics were determined in mucosal membrane preparations. In addition, alterations in crypt morphology were studied. Impaired secretory responses to VIP and forskolin were observed 4 days after irradiation (decrease of 80%). cAMP analog-stimulated I scresponses were unchanged. In isolated crypts, VIP- and forskolin-stimulated cAMP accumulation was markedly reduced by 80 and 50%, respectively. VIP-stimulated AC activity and VIP receptor number were decreased in membrane preparations. No major change of cellularity was associated with these functional alterations. In conclusion, the decreased secretory responses to VIP of rat colon are associated with reduced cAMP accumulation, decreased AC activity, and diminution of VIP receptor numbers without a marked decrease of crypt cell number.

Neuromodulation of ion transport in porcine distal colon: NPY reduces secretory actions of leukotrienes

1995 ◽  
Vol 269 (2) ◽  
pp. R426-R431 ◽  
Author(s):  
T. R. Traynor ◽  
D. R. Brown ◽  
S. M. O'Grady
Keyword(s):  
Ion Transport ◽  
Colonic Mucosa ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Effective Concentration ◽  
Leukotriene C4 ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Half Maximal Effective Concentration

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.

Effect of the thiol-oxidizing agent diamide on NH2Cl-induced rat colonic electrolyte secretion

1993 ◽  
Vol 265 (1) ◽  
pp. C166-C170 ◽  
Author(s):  
H. Tamai ◽  
J. F. Kachur ◽  
M. B. Grisham ◽  
M. W. Musch ◽  
E. B. Chang ◽  
...  
Keyword(s):  
Colonic Mucosa ◽  
Short Circuit ◽  
Chloride Ion ◽  
Short Circuit Current ◽  
Rat Colon ◽  
Maximal Effect ◽  
Oxidizing Agent ◽  
Maximal Increase ◽  
Ussing Chambers ◽  
Electrolyte Secretion

The granulocyte-derived oxidant, monochloramine (NH2Cl), is known to stimulate chloride ion secretion in rat distal colonic mucosa mounted in Ussing chambers, through mechanisms that are sensitive and insensitive to tetrodotoxin (TTX). The possible role of intracellular thiols, in the mechanism of action of NH2Cl as a secretagogue, was evaluated with the thiol-oxidizing agent diamide and by measuring tissue sulfhydryl levels in response to NH2Cl. Serosal exposure to the antioxidant glutathione (0.25 mM), 5 min before NH2Cl (50 microM) addition, decreased the maximal effect of 50 microM NH2Cl on short-circuit current (Isc). The NH2Cl-stimulated increase in Isc was not affected by mucosal amiloride (5 microM). Pretreatment with 0.1 mM diamide shortened the lag period before the increase in Isc in response to NH2Cl, but it did not affect the maximal increase in Isc. Although TTX (0.5 microM) increased the lag time for achievement of the maximal Isc response to NH2Cl, the neurotoxin did not inhibit the effect of diamide, suggesting that diamide acts primarily on the nonneural component of NH2Cl-stimulated secretion. Incubation of colonic mucosa with NH2Cl, with or without diamide, decreased cellular acid-soluble sulfhydryl concentrations. Taken together, the results support a role for epithelial cell thiols in NH2Cl-stimulated electrolyte secretion by the rat colon.

Brain natriuretic peptide stimulates K and Cl secretion across porcine distal colon epithelium

1991 ◽  
Vol 260 (4) ◽  
pp. C750-C755 ◽  
Author(s):  
T. R. Traynor ◽  
S. M. O'Grady
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Ringer Solution ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
The Difference ◽  
Distal Colon Epithelium

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.

Galanin-induced alteration of electrolyte transport in the rat intestine

1992 ◽  
Vol 263 (4) ◽  
pp. G502-G507
Author(s):  
T. Kiyohara ◽  
M. Okuno ◽  
H. Ishikawa ◽  
T. Nakanishi ◽  
Y. Shinomura ◽  
...  
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Electrical Field Stimulation ◽  
Distal Colon ◽  
Rat Colon ◽  
Chloride Absorption ◽  
Neural Transmission ◽  
36Cl Fluxes ◽  
Intestinal Ion Transport

Effects of rat and porcine galanin on rat intestinal ion transport were examined in vitro. In the rat distal colon, a sustained increase in short-circuit current (Isc) was produced by the serosal addition of rat galanin at a concentration as low as 10(-9) M, and a maximal increment was observed at 10(-7) M. Porcine galanin was approximately 100 times less potent than rat galanin. In the rat jejunum, rat galanin produced only a slight and transient decrease in basal Isc. The response to rat galanin was not influenced by atropine, hexamethonium, or amiloride, but was virtually abolished by tetrodotoxin or furosemide. Rat galanin did not significantly influence the increase in Isc elicited by electrical field stimulation in the rat colon and jejunum. Transmural unidirectional 22Na and 36Cl fluxes in the rat colonic mucosa were measured under short-circuited conditions, and rat galanin significantly decreased net sodium and net chloride absorption. These findings suggest that galanin acts as a secretory modulator in the rat colon via noncholinergic neural transmission.

Adaptation of stress-induced mucosal pathophysiology in rat colon involves opioid pathways

2001 ◽  
Vol 281 (1) ◽  
pp. G124-G128 ◽  
Author(s):  
Derrick A. Yates ◽  
Javier Santos ◽  
Johan D. Söderholm ◽  
Mary H. Perdue
Keyword(s):  
Acute Stress ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Rat Colon ◽  
Opioid Antagonists ◽  
Adaptive Responses ◽  
Ussing Chambers ◽  
Ion Secretion ◽  
Mucosal Changes ◽  
Wistar Kyoto

Acute stress increases ion secretion and permeability of rat colonic epithelium. However, it is not known if stress-induced mucosal changes are subject to adaptation. Wistar-Kyoto rats were exposed to either continuous water-avoidance stress (CS) for 60 min or intermittent stress (IS) for three 20-min periods. Distal colonic segments were mounted in Ussing Chambers, and ion-transport [short-circuit current ( I sc)] and permeability [conductance and flux of horseradish peroxidase (HRP)] parameters were measured. CS significantly increased I sc, conductance, and HRP flux compared with control values. In contrast, in IS rats these variables were similar to those in nonstressed controls. To study the pathways involved in IS-induced adaptation, rats were pretreated intraperitoneally with the opioid antagonists naloxone or methylnaloxone. Opioid antagonists had no effect on values in control or CS rats. However, in the IS group, naloxone and methylnaloxone reversed the adaptive responses, and all variables increased to CS values. We conclude that stress-induced colonic mucosal pathophysiology is subject to rapid adaptation, which involves opioid pathways.

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
Keyword(s):  
Ion Transport ◽  
Bile Acids ◽  
Phorbol Ester ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Fluid Secretion ◽  
Secretory Response ◽  
Ussing Chambers ◽  
Cl Secretion

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.

Cyclic nucleotide-gated cation channels mediate sodium and calcium influx in rat colon

2000 ◽  
Vol 278 (2) ◽  
pp. C336-C343 ◽  
Author(s):  
W. Qiu ◽  
B. Lee ◽  
M. Lancaster ◽  
W. Xu ◽  
S. Leung ◽  
...  
Keyword(s):  
Cyclic Nucleotide ◽  
Calcium Absorption ◽  
Calcium Influx ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Proximal Colon ◽  
Cation Channels ◽  
Rat Colon ◽  
Sodium Absorption

We found mRNA for the three isoforms of the cyclic nucleotide-gated nonselective cation channel expressed in the mucosal layer of the rat intestine from the duodenum to the colon and in intestinal epithelial cell lines in culture. Because these channels are permeable to sodium and calcium and are stimulated by cGMP or cAMP, we measured 8-bromo-cGMP-stimulated sodium-mediated short-circuit current ( I sc) in proximal and distal colon and unidirectional45Ca2+fluxes in proximal colon to determine whether these channels could mediate transepithelial sodium and calcium absorption across the colon. Sodium-mediated I sc, stimulated by 8-bromo-cGMP, were inhibited by dichlorobenzamil and l-cis-diltiazem, blockers of cyclic nucleotide-gated cation channels, suggesting that these ion channels can mediate transepithelial sodium absorption. Sodium-mediated I sc and net transepithelial45Ca2+absorption were stimulated by heat-stable toxin from Escherichia coli that increases cGMP. Addition of l-cis-diltiazem inhibited the enhanced transepithelial absorption of both ions. These results suggest that cyclic nucleotide-gated cation channels simultaneously increase net sodium and calcium absorption in the colon of the rat.

Effect ofE. coliheat-stable enterotoxin on colonic transport in guanylyl cyclase C receptor-deficient mice

2001 ◽  
Vol 280 (2) ◽  
pp. G216-G221 ◽  
Author(s):  
Alan N. Charney ◽  
Richard W. Egnor ◽  
Jesline T. Alexander-Chacko ◽  
Valentin Zaharia ◽  
Elizabeth A. Mann ◽  
...  
Keyword(s):  
Guanylyl Cyclase ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Proximal Colon ◽  
Guanylyl Cyclase C ◽  
Ussing Chambers ◽  
Heat Stable ◽  
Deficient Mice ◽  
Colonic Transport

We studied the functional importance of the colonic guanylyl cyclase C (GCC) receptor in GCC receptor-deficient mice. Mice were anesthetized with pentobarbital sodium, and colon segments were studied in Ussing chambers in HCO3−Ringer under short-circuit conditions. Receptor-deficient mouse proximal colon exhibited similar net Na+absorption, lower net Cl−absorption, and a negative residual ion flux ( JR), indicating net HCO3−absorption compared with that in normal mice. In normal mouse proximal colon, mucosal addition of 50 nM Escherichia coli heat-stable enterotoxin (STa) increased the serosal-to-mucosal flux of Cl−( Js→mCl) and decreased net Cl−flux ( JnetCl) accompanied by increases in short-circuit current ( Isc), potential difference (PD), and tissue conductance ( G). Serosal STa had no effect. In distal colon neither mucosal nor serosal STa affected ion transport. In receptor-deficient mice, neither mucosal nor serosal 500 nM STa affected electrolyte transport in proximal or distal colon. In these mice, 1 mM 8-bromo-cGMP produced changes in proximal colon Js→mCland JnetCl, Isc, PD, G, and JRsimilar to mucosal STa addition in normal mice. We conclude that the GCC receptor is necessary in the mouse proximal colon for a secretory response to mucosal STa.

Suppression of coupled Na-Cl absorption by aldosterone and dexamethasone in rat distal colon in vitro

1984 ◽  
Vol 246 (6) ◽  
pp. F785-F793 ◽  
Author(s):  
R. D. Perrone ◽  
S. L. Jenks
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Rat Colon ◽  
Na Transport ◽  
Unidirectional Flux ◽  
Rat Distal Colon ◽  
Marked Suppression ◽  
Stimulation Of

Basal Na absorption in the rat colon is coupled to that of Cl in an electroneutral fashion. We previously determined that aldosterone or dexamethasone induces amiloride-sensitive mucosal-to-serosal Na flux approximately equal to the amiloride-sensitive short-circuit current in rat distal colon in vitro. However, the effect of these steroids on coupled Na-Cl absorption was not examined. For this purpose, we determined the unidirectional flux of Na and Cl in voltage-clamped distal colon segments from rats treated with aldosterone or dexamethasone. Amiloride was used as a probe for conductive Na absorption, and acetazolamide and Cl-free solutions were used as probes for coupled Na-Cl absorption. Our results indicate that the nature of colonic Na absorption is markedly changed after treatment with these steroids. In contrast to findings in the untreated rat, colonic Na absorption after treatment with aldosterone or dexamethasone was largely independent of the presence of Cl. Net Cl absorption and acetazolamide sensitivity were both greatly diminished. Thus, aldosterone and dexamethasone have multiple effects on Na transport in rat distal colon. In addition to the stimulation of conductive Na absorption by aldosterone, an effect well described in other epithelia, there is marked suppression of coupled Na-Cl absorption. Dexamethasone was less effective in suppressing Cl absorption but equally effective in stimulating conductive Na absorption. These steroid effects were greater in the terminal 1-2 cm of the rat colon.

Low-dose glucocorticoids maintain Na-H exchange in distal colon of adrenalectomized rats

1991 ◽  
Vol 261 (3) ◽  
pp. F545-F553 ◽  
Author(s):  
C. P. Bastl ◽  
L. Bressler ◽  
G. Schulman ◽  
M. Mendez ◽  
E. J. Cragoe
Keyword(s):  
Short Circuit ◽  
In Vitro Study ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Ion Flux ◽  
Rat Colon ◽  
Anion Secretion ◽  
Stimulation Of

With in vivo perfusion we demonstrated that physiological doses of glucocorticoids restore Na and Cl absorption in adrenalectomized rat colon. The absorption is spironolactone and amiloride resistant and is inhibited by the Na-H inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), suggesting that glucocorticoids modulate Na-H antiport. The present in vitro study examines pathways mediated by glucocorticoids in adrenalectomized rat distal colon and rectum. In vivo administration of 2.5 micrograms/100 g body wt dexamethasone did not alter serosal-to-mucosal flux or tissue electrical parameters but restored mucosal-to-serosal flux and net Na and Cl absorption within 2–3 h of administration to levels found in intact rat colon. Transport was not inhibited by 10(-5) M amiloride but was eliminated by 10(-5) M EIPA. After 26 h of dexamethasone, an amiloride-resistant short-circuit current was stimulated, accompanied by increased residual ion flux in rectum, but not distal colon, suggesting that a delayed or secondary effect of glucocorticoids is stimulation of electrogenic anion secretion. Thus adrenalectomy reduces net ion flux in distal colon by its effect on electroneutral mucosal-to-serosal NaCl flux. Small doses of glucocorticoids completely ameliorate this effect via stimulation of the Na-H antiport. Glucocorticoids maintain basal electroneutral NaCl absorption in distal rat colon.

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