Skip to content

Study · Animal study (in vivo) · mouse · 2021

6 results

Inhibition of Na+ /H+ exchanger isoform 3 improves gut fluidity and alkalinity in cystic fibrosis transmembrane conductance regulator-deficient and F508del mutant mice.

Tan Q, di Stefano G, Tan X, Renjie X, Römermann D, Talbot SR, Seidler UE

British journal of pharmacology2 Feb 2021Cited by 26 (Europe PMC)

PMID33179259 (opens in a new tab)DOI10.1111/bph.15323 (opens in a new tab)PepBankPUB-33179259
Publisher pagePubMedAsk about this study
Jump to 6 results

Summary

Background and purposeConstipation and intestinal obstructive episodes are major health problems in cystic fibrosis (CF) patients. Three FDA-approved drugs against constipation-prone irritable bowel syndrome were tested for their ability to increase luminal fluidity and alkalinity in cystic fibrosis transmembrane conductance regulator (CFTR) null (cftr-/- ) and F508del mutant (F508delmut/mut ) murine intestine.Experimental approachGuanylate cyclase C agonist linaclotide, PGE1 analogue lubiprostone and intestine-specific NHE3 inhibitor tenapanor were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anaesthetized cftr-/- , F508delmut/mut and WT mice. Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration.Key resultsBasal jejunal fluid absorptive rates were significantly higher and basal HCO3- output was significantly lower in cftr-/- and F508delmut/mut compared to WT mice. In cftr-/- and F508delmut/mut mice, all three drugs significantly inhibited the fluid absorptive rate and increased alkaline output in the jejunum and tenapanor and lubiprostone, but not linaclotide, in the colon. After tenapanor pre-incubation, linaclotide elicited a robust fluid secretory response in WT jejunum, while no further change in absorptive rates was observed in cftr-/- and F508delmut/mut jejunum, suggesting that the increase in gut fluidity and alkalinity by linaclotide in CF gut is mediated via NHE3 inhibition. Lubiprostone also inhibited fluid absorption in cftr-/- and F508delmut/mut jejunum via NHE3 inhibition but had a residual NHE3-independent effect.Conclusion and implicationsLinaclotide, lubiprostone and tenapanor reduced fluid absorption and increased alkaline output in the CF gut. Their application may ameliorate constipation and reduce obstructive episodes in CF patients.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In CFTR-null and F508del mutant mice, linaclotide significantly inhibited jejunal fluid absorption.

    In plain wordsIn mice with CFTR deficiency or mutation, linaclotide reduced fluid absorption in the jejunum.

    Peptide
    Linaclotide
    Outcome
    DecreaseJejunal fluid absorption
    Study

    micen: not reported in source

    CFTR-null and F508del mutant mice
    Comparator
    Before drug perfusion
    Outcome group
    Bowel Function · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In cftr-/- and F508delmut/mut mice, all three drugs significantly inhibited the fluid absorptive rate and increased alkaline output in the jejunum and tenapanor and lubiprostone, but not linaclotide, in the colon.
    2 context sentences
    Summary · context
    were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anaesthetized cftr-/- , F508delmut/mut and WT mice.
    Summary · context
    Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In CFTR-null and F508del mutant mice, linaclotide significantly increased jejunal alkaline output.

    In plain wordsIn mice with CFTR deficiency or mutation, linaclotide increased alkaline output in the jejunum.

    Peptide
    Linaclotide
    Outcome
    IncreaseJejunal alkaline output
    Study

    micen: not reported in source

    CFTR-null and F508del mutant mice
    Comparator
    Before drug perfusion
    Outcome group
    Bowel Function · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In cftr-/- and F508delmut/mut mice, all three drugs significantly inhibited the fluid absorptive rate and increased alkaline output in the jejunum and tenapanor and lubiprostone, but not linaclotide, in the colon.
    2 context sentences
    Summary · context
    were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anaesthetized cftr-/- , F508delmut/mut and WT mice.
    Summary · context
    Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In CFTR-null and F508del mutant mice, linaclotide did not significantly inhibit colonic fluid absorption.

    In plain wordsIn mice with CFTR deficiency or mutation, linaclotide did not significantly reduce fluid absorption in the colon.

    Peptide
    Linaclotide
    Outcome
    No significant changeColonic fluid absorption
    Study

    micen: not reported in source

    CFTR-null and F508del mutant mice
    Comparator
    Before drug perfusion
    Outcome group
    Bowel Function · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In cftr-/- and F508delmut/mut mice, all three drugs significantly inhibited the fluid absorptive rate and increased alkaline output in the jejunum and tenapanor and lubiprostone, but not linaclotide, in the colon.
    2 context sentences
    Summary · context
    were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anaesthetized cftr-/- , F508delmut/mut and WT mice.
    Summary · context
    Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In CFTR-null and F508del mutant mice, linaclotide did not significantly increase colonic alkaline output.

    In plain wordsIn mice with CFTR deficiency or mutation, linaclotide did not significantly increase alkaline output in the colon.

    Peptide
    Linaclotide
    Outcome
    No significant changeColonic alkaline output
    Study

    micen: not reported in source

    CFTR-null and F508del mutant mice
    Comparator
    Before drug perfusion
    Outcome group
    Bowel Function · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In cftr-/- and F508delmut/mut mice, all three drugs significantly inhibited the fluid absorptive rate and increased alkaline output in the jejunum and tenapanor and lubiprostone, but not linaclotide, in the colon.
    2 context sentences
    Summary · context
    were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anaesthetized cftr-/- , F508delmut/mut and WT mice.
    Summary · context
    Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In WT mice after tenapanor pre-incubation, linaclotide elicited a robust jejunal fluid secretory response.

    In plain wordsIn mice after tenapanor exposure, adding linaclotide increased fluid secretion in the normal jejunum.

    Peptide
    Linaclotide
    Outcome
    IncreaseFluid secretion after tenapanor
    Study

    micen: not reported in source

    WT mice after tenapanor pre-incubation
    Comparator
    After tenapanor pre-incubation, before added linaclotide
    Outcome group
    Bowel Function · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    After tenapanor pre-incubation, linaclotide elicited a robust fluid secretory response in WT jejunum
    2 context sentences
    Summary · context
    were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anaesthetized cftr-/- , F508delmut/mut and WT mice.
    Summary · context
    Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration.
  6. 06AnimalAnimal study (in vivo)Efficacy outcome

    In CFTR-null and F508del mutant mice after tenapanor pre-incubation, linaclotide produced no further change in jejunal absorptive rates.

    In plain wordsIn mice with CFTR deficiency or mutation after tenapanor exposure, adding linaclotide did not further change jejunal fluid absorption.

    Peptide
    Linaclotide
    Outcome
    No significant changeFluid absorption after tenapanor
    Study

    micen: not reported in source

    CFTR-null and F508del mutant mice
    Comparator
    After tenapanor pre-incubation, before added linaclotide
    Outcome group
    Bowel Function · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    After tenapanor pre-incubation, linaclotide elicited a robust fluid secretory response in WT jejunum, while no further change in absorptive rates was observed in cftr-/- and F508delmut/mut jejunum
    2 context sentences
    Summary · context
    were perfused through a ~3 cm jejunal, proximal or mid-distal colonic segment in anaesthetized cftr-/- , F508delmut/mut and WT mice.
    Summary · context
    Net fluid balance was determined gravimetrically and alkaline output by pH-stat back titration.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 1

    27 Oct 2026, 16:34 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

PepBank is a research reference. Talk to a doctor before you use any peptide.