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Study · Ex vivo tissue · 2026

8 results

Inotropic effects of retatrutide in isolated human atrial preparations.

Neumann J, Ahlrep U, Hofmann B, Gergs U

Naunyn-Schmiedeberg's archives of pharmacology4 Jul 2025Cited by 4 (Europe PMC)

PMID40613938 (opens in a new tab)PMCIDPMC12894140 (opens in a new tab)DOI10.1007/s00210-025-04421-3 (opens in a new tab)PepBankPUB-40613938
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Summary

Retatrutide (LY3437943) was developed as a drug to treat type 2 diabetes and obesity. Retatrutide, a not endogenously occurring peptide, stimulated the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR), and the glucagon-like peptide-1 receptor (GLP-1R) in cell cultures; increased the activity of adenylyl cyclases (AC); and thus augmented the 3',5' cyclic adenosine monophosphate (cAMP) levels. We tested the hypothesis that retatrutide increased force of contraction (FOC) in human right atrial preparations (HAP) from adult patients. HAP were obtained during open heart surgery from patients who suffered from severe coronary heart disease. We noted that cumulatively applied retatrutide starting at 10 nM (up to 100 nM the highest concentration tested) elevated FOC in HAP in a concentration- and time-dependent manner. In the additional presence of the phosphodiesterase III inhibitor cilostamide (1 µM), retatrutide was more potent and more effective to increase FOC in HAP. Under these conditions, retatrutide shortened the time of muscle relaxation in HAP. These positive inotropic effects of glucagon were diminished by a GLP1-R antagonist, by a GIPR antagonist, and by a CGCR antagonist but not by propranolol, an antagonist at β-adrenoceptors. The effects of retatrutide on FOC were also reduced by 100 nM ryanodine, an inhibitor of the ryanodine receptor in the sarcoplasmic reticulum, by 1 µM carbachol, a M-cholinoceptor agonist, and by 1 µM (-)-N6-phenylisopropyladenosine, an A1-adenosine receptor agonist. Summarily, we suggest that retatrutide enlarged FOC in HAP via the cAMP system through its cognate receptors.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

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

  1. 01LabEx vivo tissueEfficacy outcome

    In isolated human right atrial preparations, cumulatively applied retatrutide from 10 nM up to 100 nM increased force of contraction in a concentration- and time-dependent manner.

    In plain wordsIn lab tests on human heart tissue, retatrutide increased the force of contraction as concentration and time increased.

    Peptide
    Retatrutide
    Outcome
    IncreaseForce of contraction
    Study

    humann: not reported in source

    Isolated human right atrial preparations
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    10-100 nMAs given in this study (human).

    Source sentences

    Summary
    We noted that cumulatively applied retatrutide starting at 10 nM (up to 100 nM the highest concentration tested) elevated FOC in HAP in a concentration- and time-dependent manner.
    2 context sentences
    Summary · context
    We tested the hypothesis that retatrutide increased force of contraction (FOC) in human right atrial preparations (HAP) from adult patients.
    Summary · context
    HAP were obtained during open heart surgery from patients who suffered from severe coronary heart disease.
  2. 02LabEx vivo tissueEfficacy outcome

    In isolated human right atrial preparations, with the phosphodiesterase III inhibitor cilostamide present, retatrutide was more potent and more effective in increasing force of contraction.

    In plain wordsIn lab tests on human heart tissue, retatrutide raised contraction force more strongly when cilostamide was also present.

    Peptide
    Retatrutide
    Outcome
    IncreaseForce of contraction with cilostamide
    Study

    humann: not reported in source

    Isolated human right atrial preparations
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In the additional presence of the phosphodiesterase III inhibitor cilostamide (1 µM), retatrutide was more potent and more effective to increase FOC in HAP.
    2 context sentences
    Summary · context
    We tested the hypothesis that retatrutide increased force of contraction (FOC) in human right atrial preparations (HAP) from adult patients.
    Summary · context
    HAP were obtained during open heart surgery from patients who suffered from severe coronary heart disease.
  3. 03LabEx vivo tissueEfficacy outcome

    In isolated human right atrial preparations, with cilostamide present, retatrutide shortened the time of muscle relaxation.

    In plain wordsIn lab tests on human heart tissue, retatrutide with cilostamide shortened muscle relaxation time.

    Peptide
    Retatrutide
    Outcome
    DecreaseMuscle relaxation time
    Study

    humann: not reported in source

    Isolated human right atrial preparations
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Under these conditions, retatrutide shortened the time of muscle relaxation in HAP.
    2 context sentences
    Summary · context
    We tested the hypothesis that retatrutide increased force of contraction (FOC) in human right atrial preparations (HAP) from adult patients.
    Summary · context
    HAP were obtained during open heart surgery from patients who suffered from severe coronary heart disease.
  4. 04LabEx vivo tissueMechanism

    In isolated human right atrial preparations, positive inotropic effects (named as effects of glucagon in the abstract) were diminished by GLP-1R, GIPR and GCGR antagonists.

    In plain wordsIn lab tests on human heart tissue, blocking any of the three receptors weakened the contraction effect.

    Peptide
    Retatrutide
    Outcome
    DecreaseInotropic effect with GLP-1R, GIPR and GCGR antagonists
    Study

    humann: not reported in source

    Isolated human right atrial preparations
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    These positive inotropic effects of glucagon were diminished by a GLP1-R antagonist, by a GIPR antagonist, and by a CGCR antagonist
    2 context sentences
    Summary · context
    We tested the hypothesis that retatrutide increased force of contraction (FOC) in human right atrial preparations (HAP) from adult patients.
    Summary · context
    HAP were obtained during open heart surgery from patients who suffered from severe coronary heart disease.
  5. 05LabEx vivo tissueMechanism

    In isolated human right atrial preparations, positive inotropic effects (named as effects of glucagon in the abstract) were not diminished by propranolol, a beta-adrenoceptor antagonist.

    In plain wordsIn lab tests on human heart tissue, propranolol did not weaken the contraction effect.

    Peptide
    Retatrutide
    Outcome
    No significant changeInotropic effect with propranolol
    Study

    humann: not reported in source

    Isolated human right atrial preparations
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    but not by propranolol, an antagonist at β-adrenoceptors.
    2 context sentences
    Summary · context
    We tested the hypothesis that retatrutide increased force of contraction (FOC) in human right atrial preparations (HAP) from adult patients.
    Summary · context
    HAP were obtained during open heart surgery from patients who suffered from severe coronary heart disease.
  6. 06LabEx vivo tissueMechanism

    In isolated human right atrial preparations, the effects of retatrutide on force of contraction were reduced by ryanodine.

    In plain wordsIn lab tests on human heart tissue, ryanodine reduced the contraction effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    DecreaseInotropic effect with ryanodine
    Study

    humann: not reported in source

    Isolated human right atrial preparations
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The effects of retatrutide on FOC were also reduced by 100 nM ryanodine, an inhibitor of the ryanodine receptor in the sarcoplasmic reticulum
    2 context sentences
    Summary · context
    We tested the hypothesis that retatrutide increased force of contraction (FOC) in human right atrial preparations (HAP) from adult patients.
    Summary · context
    HAP were obtained during open heart surgery from patients who suffered from severe coronary heart disease.
  7. 07LabEx vivo tissueMechanism

    In isolated human right atrial preparations, the effects of retatrutide on force of contraction were reduced by the M-cholinoceptor agonist carbachol.

    In plain wordsIn lab tests on human heart tissue, carbachol reduced the contraction effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    DecreaseInotropic effect with carbachol
    Study

    humann: not reported in source

    Isolated human right atrial preparations
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    by 1 µM carbachol, a M-cholinoceptor agonist
    2 context sentences
    Summary · context
    We tested the hypothesis that retatrutide increased force of contraction (FOC) in human right atrial preparations (HAP) from adult patients.
    Summary · context
    HAP were obtained during open heart surgery from patients who suffered from severe coronary heart disease.
  8. 08LabEx vivo tissueMechanism

    In isolated human right atrial preparations, the effects of retatrutide on force of contraction were reduced by an A1-adenosine receptor agonist.

    In plain wordsIn lab tests on human heart tissue, an adenosine receptor agonist reduced the contraction effect of retatrutide.

    Peptide
    Retatrutide
    Outcome
    DecreaseInotropic effect with A1-adenosine receptor agonist
    Study

    humann: not reported in source

    Isolated human right atrial preparations
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    and by 1 µM (-)-N6-phenylisopropyladenosine, an A1-adenosine receptor agonist
    2 context sentences
    Summary · context
    We tested the hypothesis that retatrutide increased force of contraction (FOC) in human right atrial preparations (HAP) from adult patients.
    Summary · context
    HAP were obtained during open heart surgery from patients who suffered from severe coronary heart disease.

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, 18:17 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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