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Study · Ex vivo tissue · mouse · 2025

10 results

Contractile effects of retatrutide in isolated mouse atrial preparations.

Neumann J, Ahlrep U, Hofmann B, Gergs U

Naunyn-Schmiedeberg's archives of pharmacology4 Jun 2025Cited by 5 (Europe PMC)

PMID40464942 (opens in a new tab)PMCIDPMC12678479 (opens in a new tab)DOI10.1007/s00210-025-04335-0 (opens in a new tab)PepBankPUB-40464942
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Summary

When retatrutide stimulates the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R), then 3',5'cyclic adenosine monophosphate (cAMP) is increased. We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice. While 100 nM isoprenaline increased FOC, retatrutide (100 nM) failed to increase FOC in LA. In isolated mouse right atrial preparations (RA), retatrutide exerted PCE that were potentiated by 100 nM rolipram but that were antagonized by adomeglivant, a GCGR antagonist. The PCE of retatrutide but not the PCE of isoprenaline were attenuated by H89, an inhibitor of the cAMP-dependent protein kinase (PKA). The PCE of retatrutide were not weakened by the β-adrenoceptor antagonist propranolol (1 µM) but were blocked by 1 µM carbachol, an agonist at M2-cholinoceptor, and this effect was reversed by 1 µM atropine, a muscarinic receptor antagonist. Likewise, the PCE of retatrutide were blocked by 1 µM (-)-N6-phenylisopropyladenosine (PIA), an A1-adenosine receptor agonist, and this effect was reversed by 1 µM DPCPX, an adenosine A1-receptor antagonist. We conclude that retatrutide excites the beating rate in RA via GCGR, signalling via cAMP and PKA. Isoprenaline and retatrutide might increase cAMP in different compartments of the mouse sinus node.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

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

  1. 01LabEx vivo tissueActivity measurement

    In isolated mouse left atria, retatrutide 100 nM did not increase force of contraction, whereas isoprenaline 100 nM did.

    In plain wordsIn isolated mouse heart tissue, retatrutide did not raise the force of contraction, while isoprenaline did.

    Peptide
    Retatrutide
    Outcome
    No significant changeForce of contraction in left atrium
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Comparator
    Isoprenaline 100 nM
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    100 nMAs given in this study (mouse).

    Source sentences

    Summary
    While 100 nM isoprenaline increased FOC, retatrutide (100 nM) failed to increase FOC in LA.
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.
  2. 02LabEx vivo tissueActivity measurement

    In isolated mouse right atria, retatrutide had a positive chronotropic effect on the spontaneous beating rate.

    In plain wordsIn isolated mouse heart tissue, retatrutide raised the beating rate.

    Peptide
    Retatrutide
    Outcome
    IncreasePositive chronotropic effect in right atrium
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In isolated mouse right atrial preparations (RA), retatrutide exerted PCE
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.
  3. 03LabEx vivo tissueMechanism

    In isolated mouse right atria, the positive chronotropic effect of retatrutide was potentiated by 100 nM rolipram.

    In plain wordsIn isolated mouse heart tissue, the rolipram drug increased the beating-rate effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    IncreaseRetatrutide chronotropic effect with rolipram
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Comparator
    Rolipram 100 nM
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    retatrutide exerted PCE that were potentiated by 100 nM rolipram
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.
  4. 04LabEx vivo tissueMechanism

    In isolated mouse right atria, the positive chronotropic effect of retatrutide was antagonized by adomeglivant, a GCGR antagonist.

    In plain wordsIn isolated mouse heart tissue, a glucagon receptor blocker reduced the beating-rate effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    DecreaseRetatrutide chronotropic effect with adomeglivant
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Comparator
    Adomeglivant
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    but that were antagonized by adomeglivant, a GCGR antagonist.
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.
  5. 05LabEx vivo tissueMechanism

    In isolated mouse right atria, the chronotropic effect of retatrutide, but not that of isoprenaline, was attenuated by the PKA inhibitor H89.

    In plain wordsIn isolated mouse heart tissue, a PKA blocker reduced the beating-rate effect of retatrutide but not that of isoprenaline.

    Peptide
    Retatrutide
    Outcome
    DecreaseRetatrutide chronotropic effect with H89
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Comparator
    H89
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The PCE of retatrutide but not the PCE of isoprenaline were attenuated by H89, an inhibitor of the cAMP-dependent protein kinase (PKA).
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.
  6. 06LabEx vivo tissueMechanism

    In isolated mouse right atria, the chronotropic effect of retatrutide was not weakened by the β-adrenoceptor antagonist propranolol.

    In plain wordsIn isolated mouse heart tissue, the beta blocker propranolol did not weaken the beating-rate effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    No significant changeRetatrutide chronotropic effect with propranolol
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Comparator
    Propranolol 1 µM
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The PCE of retatrutide were not weakened by the β-adrenoceptor antagonist propranolol (1 µM)
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.
  7. 07LabEx vivo tissueMechanism

    In isolated mouse right atria, the chronotropic effect of retatrutide was blocked by the M2-cholinoceptor agonist carbachol.

    In plain wordsIn isolated mouse heart tissue, carbachol blocked the beating-rate effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    DecreaseRetatrutide chronotropic effect with carbachol
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Comparator
    Carbachol 1 µM
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The PCE of retatrutide were not weakened by the β-adrenoceptor antagonist propranolol (1 µM) but were blocked by 1 µM carbachol, an agonist at M2-cholinoceptor, and this effect was reversed by 1 µM atropine, a muscarinic receptor antagonist.
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.
  8. 08LabEx vivo tissueMechanism

    In isolated mouse right atria, atropine reversed the carbachol block of the chronotropic effect of retatrutide.

    In plain wordsIn isolated mouse heart tissue, atropine undid the carbachol block of the beating-rate effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    IncreaseRetatrutide chronotropic effect after carbachol with atropine
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Comparator
    Atropine 1 µM
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The PCE of retatrutide were not weakened by the β-adrenoceptor antagonist propranolol (1 µM) but were blocked by 1 µM carbachol, an agonist at M2-cholinoceptor, and this effect was reversed by 1 µM atropine, a muscarinic receptor antagonist.
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.
  9. 09LabEx vivo tissueMechanism

    In isolated mouse right atria, the chronotropic effect of retatrutide was blocked by the A1-adenosine receptor agonist PIA.

    In plain wordsIn isolated mouse heart tissue, the adenosine A1 agonist PIA blocked the beating-rate effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    DecreaseRetatrutide chronotropic effect with PIA
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Comparator
    PIA 1 µM
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Likewise, the PCE of retatrutide were blocked by 1 µM (-)-N6-phenylisopropyladenosine (PIA), an A1-adenosine receptor agonist, and this effect was reversed by 1 µM DPCPX, an adenosine A1-receptor antagonist.
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.
  10. 10LabEx vivo tissueMechanism

    In isolated mouse right atria, the adenosine A1-receptor antagonist DPCPX reversed the PIA block of the chronotropic effect of retatrutide.

    In plain wordsIn isolated mouse heart tissue, DPCPX undid the PIA block of the beating-rate effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    IncreaseRetatrutide chronotropic effect after PIA with DPCPX
    Study

    mousen: not reported in source

    isolated atrial preparations from adult CD1 mice
    Comparator
    DPCPX 1 µM
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Likewise, the PCE of retatrutide were blocked by 1 µM (-)-N6-phenylisopropyladenosine (PIA), an A1-adenosine receptor agonist, and this effect was reversed by 1 µM DPCPX, an adenosine A1-receptor antagonist.
    1 context sentence
    Summary · context
    We tested the hypothesis that retatrutide like the β-adrenoceptor agonist isoprenaline raises force of contraction (FOC) in isolated electrically driven (1 Hz) left atrial preparations (LA) and exerts positive chronotropic effects (PCE) in isolated spontaneously beating right atrial preparations (RA) from adult CD1 mice.

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

    9 Oct 2026, 19:08 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

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