Skip to content

Study · Animal study (in vivo) · mouse · 2023

4 results

Intestinal neuropod cell GUCY2C regulates visceral pain.

Barton JR, Londregan AK, Alexander TD, Entezari AA, Bar-Ad S, Cheng L, Lepore AC, Snook AE, Covarrubias M, Waldman SA

The Journal of clinical investigation15 Feb 2023Cited by 25 (Europe PMC)

PMID36548082 (opens in a new tab)PMCIDPMC9927949 (opens in a new tab)DOI10.1172/jci165578 (opens in a new tab)PepBankPUB-36548082
Download PDFPubMedAsk about this study
Jump to 4 results

Summary

Visceral pain (VP) is a global problem with complex etiologies and limited therapeutic options. Guanylyl cyclase C (GUCY2C), an intestinal receptor producing cyclic GMP(cGMP), which regulates luminal fluid secretion, has emerged as a therapeutic target for VP. Indeed, FDA-approved GUCY2C agonists ameliorate VP in patients with chronic constipation syndromes, although analgesic mechanisms remain obscure. Here, we revealed that intestinal GUCY2C was selectively enriched in neuropod cells, a type of enteroendocrine cell that synapses with submucosal neurons in mice and humans. GUCY2Chi neuropod cells associated with cocultured dorsal root ganglia neurons and induced hyperexcitability, reducing the rheobase and increasing the resulting number of evoked action potentials. Conversely, the GUCY2C agonist linaclotide eliminated neuronal hyperexcitability produced by GUCY2C-sufficient - but not GUCY2C-deficient - neuropod cells, an effect independent of bulk epithelial cells or extracellular cGMP. Genetic elimination of intestinal GUCY2C amplified nociceptive signaling in VP that was comparable with chemically induced VP but refractory to linaclotide. Importantly, eliminating GUCY2C selectively in neuropod cells also increased nociceptive signaling and VP that was refractory to linaclotide. In the context of loss of GUCY2C hormones in patients with VP, these observations suggest a specific role for neuropod GUCY2C signaling in the pathophysiology and treatment of these pain syndromes.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

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

  1. 01AnimalAnimal study (in vivo)Mechanism

    In mice with intestinal GUCY2C deletion, amplified nociceptive signaling was refractory to linaclotide.

    In plain wordsIn mice without intestinal GUCY2C, increased pain signaling did not respond to linaclotide.

    Peptide
    Linaclotide
    Outcome
    No significant changeNociceptive signaling after intestinal GUCY2C deletion
    Study

    micen: not reported in source

    Intestinal GUCY2C deletion
    Outcome group
    Pain · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Genetic elimination of intestinal GUCY2C amplified nociceptive signaling in VP that was comparable with chemically induced VP but refractory to linaclotide.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In mice with neuropod-cell GUCY2C deletion, increased nociceptive signaling and visceral pain were refractory to linaclotide.

    In plain wordsIn mice without neuropod-cell GUCY2C, increased pain signaling and visceral pain did not respond to linaclotide.

    Peptide
    Linaclotide
    Outcome
    No significant changeNociceptive signaling and visceral pain after neuropod GUCY2C deletion
    Study

    micen: not reported in source

    Neuropod-cell GUCY2C deletion
    Outcome group
    Pain · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Importantly, eliminating GUCY2C selectively in neuropod cells also increased nociceptive signaling and VP that was refractory to linaclotide.
  3. 03LabIn vitro (cells)Mechanism

    In cocultures, linaclotide eliminated neuronal hyperexcitability produced by GUCY2C-sufficient neuropod cells, independently of bulk epithelial cells or extracellular cGMP.

    In plain wordsIn cells, linaclotide eliminated the neuronal hyperexcitability produced by neuropod cells with GUCY2C.

    Peptide
    Linaclotide
    Outcome
    DecreaseNeuronal hyperexcitability with GUCY2C-sufficient neuropod cells
    Study

    n: not reported in source

    Neuropod cell-neuron coculture
    Comparator
    Hyperexcitability produced by GUCY2C-sufficient neuropod cells
    Outcome group
    Pain · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Conversely, the GUCY2C agonist linaclotide eliminated neuronal hyperexcitability produced by GUCY2C-sufficient - but not GUCY2C-deficient - neuropod cells, an effect independent of bulk epithelial cells or extracellular cGMP.
  4. 04LabIn vitro (cells)Mechanism

    In cocultures, linaclotide did not eliminate neuronal hyperexcitability produced by GUCY2C-deficient neuropod cells.

    In plain wordsIn cells, linaclotide did not eliminate neuronal hyperexcitability produced by neuropod cells without GUCY2C.

    Peptide
    Linaclotide
    Outcome
    No significant changeNeuronal hyperexcitability with GUCY2C-deficient neuropod cells
    Study

    n: not reported in source

    GUCY2C-deficient neuropod cell-neuron coculture
    Outcome group
    Pain · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Conversely, the GUCY2C agonist linaclotide eliminated neuronal hyperexcitability produced by GUCY2C-sufficient - but not GUCY2C-deficient - neuropod cells, an effect independent of bulk epithelial cells or extracellular cGMP.

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.