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Study · Animal study (in vivo) · rat · 2017

5 results

Linaclotide activates guanylate cyclase-C/cGMP/protein kinase-II-dependent trafficking of CFTR in the intestine.

Ahsan MK, Tchernychev B, Kessler MM, Solinga RM, Arthur D, Linde CI, Silos-Santiago I, Hannig G, Ameen NA

Physiological reports1 Jun 2017Cited by 47 (Europe PMC)

PMID28592587 (opens in a new tab)PMCIDPMC5471438 (opens in a new tab)DOI10.14814/phy2.13299 (opens in a new tab)PepBankPUB-28592587
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Summary

The transmembrane receptor guanylyl cyclase-C (GC-C), expressed on enterocytes along the intestine, is the molecular target of the GC-C agonist peptide linaclotide, an FDA-approved drug for treatment of adult patients with Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation. Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays. Expression and activity of GC-C/cGMP pathway components were determined by PCR, western blot, and cGMP assays. Fluid secretion as a marker of CFTR cell surface translocation was determined using in vivo rat intestinal loops. Linaclotide treatment (30 min) induced robust fluid secretion and translocation of CFTR from subapical compartments to the cell surface in rat intestinal loops. Similarly, linaclotide treatment (30 min) of T84 and CaCo-2BBe cells increased cell surface CFTR levels. Linaclotide-induced activation of the GC-C/cGMP/PKGII signaling pathway resulted in elevated intracellular cGMP and pVASPser239 phosphorylation. Inhibition or silencing of PKGII significantly attenuated linaclotide-induced CFTR trafficking to the apical membrane. Inhibition of protein kinase-A (PKA) also attenuated linaclotide-induced CFTR cell surface trafficking, implying cGMP-dependent cross-activation of PKA pathway. Together, these findings support linaclotide-induced activation of the GC-C/cGMP/PKG-II/CFTR pathway as the major pathway of linaclotide-mediated intestinal fluid secretion, and that linaclotide-dependent CFTR activation and recruitment/trafficking of CFTR from subapical vesicles to the cell surface is an important step in this process.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

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

  1. 01AnimalAnimal study (in vivo)Mechanism

    In rat intestinal loops, linaclotide induced robust fluid secretion after 30 min.

    In plain wordsIn rats, linaclotide induced intestinal fluid secretion after 30 min.

    Peptide
    Linaclotide
    Outcome
    IncreaseFluid secretion
    Study

    ratn: not reported in source

    intestinal loops
    Outcome group
    Receptor activity and mechanism · Gastrointestinal
    Studied dose
    Dose not stated · 30 minAs given in this study (rat).

    Source sentences

    Summary
    Linaclotide treatment (30 min) induced robust fluid secretion and translocation of CFTR from subapical compartments to the cell surface in rat intestinal loops.
    1 context sentence
    Summary · context
    Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In rat intestinal loops, linaclotide induced CFTR translocation from subapical compartments to the cell surface after 30 min.

    In plain wordsIn rats, linaclotide moved intestinal CFTR to the cell surface after 30 min.

    Peptide
    Linaclotide
    Outcome
    IncreaseCFTR surface translocation
    Study

    ratn: not reported in source

    intestinal loops
    Outcome group
    Receptor activity and mechanism · Gastrointestinal
    Studied dose
    Dose not stated · 30 minAs given in this study (rat).

    Source sentences

    Summary
    Linaclotide treatment (30 min) induced robust fluid secretion and translocation of CFTR from subapical compartments to the cell surface in rat intestinal loops.
    1 context sentence
    Summary · context
    Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays.
  3. 03LabIn vitro (cells)Mechanism

    In T84 and CaCo-2BBe cells, linaclotide increased cell surface CFTR after 30 min.

    In plain wordsIn cells, linaclotide increased surface CFTR after 30 min.

    Peptide
    Linaclotide
    Outcome
    IncreaseCell surface CFTR
    Study

    humann: not reported in source

    T84 and CaCo-2BBe cells
    Outcome group
    Receptor activity and mechanism · Gastrointestinal
    Studied dose
    Dose not stated · 30 minAs given in this study (human).

    Source sentences

    Summary
    Similarly, linaclotide treatment (30 min) of T84 and CaCo-2BBe cells increased cell surface CFTR levels.
    1 context sentence
    Summary · context
    Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays.
  4. 04LabOther designMechanism

    In intestinal experimental systems, linaclotide pathway activation elevated intracellular cGMP.

    In plain wordsIn lab tests, linaclotide pathway activation increased cGMP inside cells.

    Peptide
    Linaclotide
    Outcome
    IncreaseIntracellular cGMP
    Study

    n: not reported in source

    intestinal experimental systems
    Outcome group
    Receptor activity and mechanism · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Linaclotide-induced activation of the GC-C/cGMP/PKGII signaling pathway resulted in elevated intracellular cGMP and pVASPser239 phosphorylation.
    1 context sentence
    Summary · context
    Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays.
  5. 05LabOther designMechanism

    In intestinal experimental systems, linaclotide pathway activation elevated pVASP ser239 phosphorylation.

    In plain wordsIn lab tests, linaclotide pathway activation increased pVASP phosphorylation.

    Peptide
    Linaclotide
    Outcome
    IncreasepVASP phosphorylation
    Study

    n: not reported in source

    intestinal experimental systems
    Outcome group
    Receptor activity and mechanism · Gastrointestinal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Linaclotide-induced activation of the GC-C/cGMP/PKGII signaling pathway resulted in elevated intracellular cGMP and pVASPser239 phosphorylation.
    1 context sentence
    Summary · context
    Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays.

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.

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