Organic acid proton donors decrease intestinal secretion caused by enterotoxins

1981 ◽  
Vol 241 (3) ◽  
pp. G227-G234
Author(s):  
G. W. Forsyth ◽  
R. A. Kapitany ◽  
D. L. Hamilton
Keyword(s):  
Cholera Toxin ◽  
Intestinal Secretion ◽  
Fluid Secretion ◽  
Weak Acid ◽  
Aminobenzoic Acid ◽  
Control Loops ◽  
Heat Stable ◽  
Acid Proton ◽  
Proton Donors ◽  
Sodium Flux

The effects of several weak acids on the secretory actions of cholera toxin and the heat-stable enterotoxin of Escherichia coli (ST) have been examined in ligated jejunal loops in weanling pigs. Ascorbic and acetic acids had no effect, but L-lactic acid reduced the net fluid secretion caused by cholera toxin. Glutaric acid and p-aminobenzoic acid blocked net fluid secretion caused by cholera toxin or by ST. Antisecretory effects were pH dependent for p-aminobenzoic acid in this study and for nicotinic acid in a previous report (6). At a pH of 5.0, p-aminobenzoic acid treatment increased lumen-to-blood sodium flux and decreased the blood-to-lumen sodium flux caused by cholera toxin. These weak acid effects were more marked on fluid fluxes in enterotoxin-treated loops than in control loops and persisted for 20–30 min after acid removal from loops. These findings are discussed in terms of requirements for antisecretory activity and possible modes of action of antisecretory compounds.

Cholera toxin induces intestinal secretion in an acute renal failure rat model

2021 ◽  
Vol 01 ◽  
Author(s):  
Parvin Abraham ◽  
Anu Joseph ◽  
Parvathy Sreekumar ◽  
Koyikkal Karthikeya Varma ◽  
Lilly Madhavan
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Cholera Toxin ◽  
Diarrheal Disease ◽  
Intestinal Secretion ◽  
Fluid Secretion ◽  
Secretory Response ◽  
Histopathological Analysis ◽  
Intestinal Loop ◽  
Life Threatening

Background: Cholera is a life-threatening secretory diarrheal disease caused by Vibrio cholera bacterium. On the contrary, local and specific use of cholera toxin (CT) at a low concentration can cause controlled fluid secretion. In the study, we explored the secretory action of CT in the intestine of rats with acute renal failure (ARF). Methods: Closed intestinal loop experiments were performed in ARF rats treated with CT. Secreted fluid and serum were analyzed for various ¬solutes and electrolytes. The presence of K+, Na+, Cl-, urea and creatinine were monitored. Histopathology analysis was carried out to evaluate the effect of CT in liver, kidney, and intestinal tissues. Results: A reduction in the absorption of water and electrolytes was observed over time and a secretory response started to appear within hours of CT treatment. The fluid secretory response with entrapped electrolytes was profound in ARF rats. Histopathological analysis of CT exposed tissues revealed that apart from the tissue damage produced by acute renal failure, no CT induced cellular changes occurred. Conclusion: CT can be used as a secretagogue to induce fluid and electrolyte secretion in ARF rats. However, effective measures should be taken to avoid CT induced acidosis.

Effects of Tropisetron, a 5-Hydroxytryptamine Type 3 Receptor Blocker, on Intestinal Secretion Induced by Cholera Toxin or Deoxycholic Acid in Rabbits In Vivo

1993 ◽  
Vol 21 (6) ◽  
pp. 323-333 ◽  
Author(s):  
P K Bardhan ◽  
A S MH Rahman ◽  
S Islam ◽  
M Rahman ◽  
K Gyr
Keyword(s):  
Cholera Toxin ◽  
Deoxycholic Acid ◽  
Intraperitoneal Administration ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Intestinal Secretion ◽  
Fluid Secretion ◽  
Receptor Blocker ◽  
Type 3

It has been suggested that 5-hydroxytryptamine is involved in the pathogenesis of various intestinal hypersecretory states including cholera. In this study, the effect of tropisetron (ICS 205-930), a specific 5-hydroxytryptamine type-3 receptor blocker, on jejunal and colonic fluid secretion induced respectively by cholera toxin and deoxycholic acid was investigated in rabbits using isolated loops of intestine in vivo. Marked fluid accumulation in both the jejunal and colonic loops was observed after exposure to cholera toxin and deoxycholic acid respectively. Elevation of jejunal and colonic mucosal cyclic adenosine monophosphate concentrations was also noted. Intraperitoneal administration of tropisetron dose-dependent inhibited jejunal secretion induced by cholera toxin. In contrast, no significant anti-secretory effect of tropisetron was observed against colonic secretion induced by deoxycholic acid. Tropisetron did not affect elevated mucosal cyclic adenosine monophosphate concentrations. The inhibitory effect of tropisetron on intestinal secretion induced by cholera toxin, which was independent of cyclic adenosine monophosphate formation, suggests that 5- hydroxytryptamine plays an important role in this type of secretion.

Failure to reverse cholera toxin induced intestinal secretion by agents which decrease mucosal cAMP

1979 ◽  
Vol 57 (9) ◽  
pp. 1004-1010 ◽  
Author(s):  
G. W. Forsyth ◽  
D. L. Hamilton ◽  
A. Scoot ◽  
K. E. Goertz ◽  
R. A. Kapitany
Keyword(s):  
Escherichia Coli ◽  
Adenylate Cyclase ◽  
Cholera Toxin ◽  
Intestinal Mucosa ◽  
Cyclic Nucleotide ◽  
Intestinal Secretion ◽  
Camp Concentration ◽  
Pharmacological Agents ◽  
Heat Stable ◽  
Toxin Secretion

The feasibility of reducing intestinal secretion by the use of agents which decrease intestinal mucosal cAMP concentration has been investigated in the weanling pig and the rabbit. Three different agents for decreasing mucosal cAMP concentration were studied. The cyclic nucleotide phosphodiesterase activator, imidazole, significantly reduced mucosal cAMP concentrations only in the weanling pig. Intraluminal 2′-deoxyadenosine-3′-AMP inhibited adenylate cyclase and caused a decrease in mucosal cAMP concentration in both the pig and the rabbit. The introduction of the heat-stable enterotoxin of Escherichia coli into pig jejunal segments also gave lowered mucosal cAMP concentrations. While these three agents effectively reduced cAMP concentrations in intestinal mucosa, they were ineffective in reducing the net fluid secretory effects of cholera toxin. Secretion caused by cholera toxin apparently persists independent of the temporary changes in cAMP concentration which can be induced by pharmacological agents.

scholarly journals Intestinal Enteroids Model Guanylate Cyclase C-Dependent Secretion Induced by Heat-Stable Enterotoxins

2016 ◽  
Vol 84 (10) ◽  
pp. 3083-3091 ◽  
Author(s):  
Amanda M. Pattison ◽  
Erik S. Blomain ◽  
Dante J. Merlino ◽  
Fang Wang ◽  
Mary Ann S. Crissey ◽  
...  
Keyword(s):  
High Throughput ◽  
Guanylate Cyclase ◽  
High Throughput Screening ◽  
Molecular Mechanisms ◽  
Diarrheal Disease ◽  
Intestinal Secretion ◽  
Fluid Secretion ◽  
Heat Stable ◽  
Guanylate Cyclase C ◽  
Signaling Axis

EnterotoxigenicEscherichia coli(ETEC) causes ∼20% of the acute infectious diarrhea (AID) episodes worldwide, often by producing heat-stable enterotoxins (STs), which are peptides structurally homologous to paracrine hormones of the intestinal guanylate cyclase C (GUCY2C) receptor. While molecular mechanisms mediating ST-induced intestinal secretion have been defined, advancements in therapeutics have been hampered for decades by the paucity of disease models that integrate molecular and functional endpoints amenable to high-throughput screening. Here, we reveal that mouse and human intestinal enteroids in three-dimensionalex vivocultures express the components of the GUCY2C secretory signaling axis. ST and its structural analog, linaclotide, an FDA-approved oral secretagog, induced fluid accumulation quantified simultaneously in scores of enteroid lumens, recapitulating ETEC-induced intestinal secretion. Enteroid secretion depended on canonical molecular signaling events responsible for ETEC-induced diarrhea, including cyclic GMP (cGMP) produced by GUCY2C, activation of cGMP-dependent protein kinase (PKG), and opening of the cystic fibrosis transmembrane conductance regulator (CFTR). Importantly, pharmacological inhibition of CFTR abrogated enteroid fluid secretion, providing proof of concept for the utility of this model to screen antidiarrheal agents. Intestinal enteroids offer a unique model, integrating the GUCY2C signaling axis and luminal fluid secretion, to explore the pathophysiology of, and develop platforms for, high-throughput drug screening to identify novel compounds to prevent and treat ETEC diarrheal disease.

On the Role of Intramural Nerves in the Pathogenesis of Cholera Toxin-induced Intestinal Secretion

1981 ◽  
Vol 16 (3) ◽  
pp. 377-384 ◽  
Author(s):  
J. Cassuto ◽  
M. Jodal ◽  
R. Tuttle ◽  
O. Lundgren
Keyword(s):  
Cholera Toxin ◽  
Intestinal Secretion

scholarly journals Does enteropathogenic Escherichia coli produce heat-labile enterotoxin, heat-stable enterotoxins a or b, or cholera toxin A subunits?

1984 ◽  
Vol 46 (2) ◽  
pp. 612-614 ◽  
Author(s):  
S A Long-Krug ◽  
C S Weikel ◽  
K T Tiemens ◽  
E L Hewlett ◽  
M M Levine ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cholera Toxin ◽  
Enteropathogenic Escherichia Coli ◽  
Toxin A ◽  
Heat Stable ◽  
Heat Labile

Inhibition of Escherichia coli heat-stable enterotoxin by indomethacin and chlorpromazine

1980 ◽  
Vol 29 (3) ◽  
pp. 908-913
Author(s):  
R N Greenberg ◽  
F Murad ◽  
B Chang ◽  
D C Robertson ◽  
R L Guerrant
Keyword(s):  
Escherichia Coli ◽  
Guanylate Cyclase ◽  
Fluid Secretion ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Enterotoxigenic Escherichia Coli ◽  
Fluid Accumulation ◽  
Intestinal Tissue ◽  
Suckling Mice ◽  
Heat Stable

Purified heat-stable enterotoxin (ST) from a procine strain of enterotoxigenic Escherichia coli activates quanylate cyclase in particulate fractions of rat intestinal tissue and induces fluid accumulation in suckling mice. These effects of ST were examined in the presence of either indomethacin or chlorpromazine. We also examined the effects of these two drugs on fluid accumulation in suckling mice induced by the 8-bromo analog of cyclic guanosine monophosphate. Either indomethacin or chlorpromazine reduced ST activation of guanylate cyclase. Both drugs also reduced intestinal fluid accumulation in suckling mice that resulted from submaximal doses of ST (both P < 0.001). However, there was no reduction in fluid secretion by either drug when a maximally effective dose of ST was used, suggesting that inhibition of fluid secretion by both drugs can be overcome by increasing the ST dose and that a threshold level of guanylate cyclase activity results in maximal secretory response. Both drugs also reduced basal guanylate cylase activity in rat intestinal tissue and fluid secreton in suckling mice. Chlorpromazine also reduced intestinal secretion mediated by 8-bromo cyclic guanosine monophosphate (P < 0.001). These findings indicate that chlorpromazine interferes with the effects of ST both before and after its activation of guanylate cyclase, whereas indomethacin interfers with ST only before its activation of guanylate cyclase.

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