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Anti-inflammatory and antinociceptive activities of glucagon-like peptides: evaluation of their actions on serotonergic, nitrergic, and opioidergic systems

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Abstract

Rationale

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are gut derived hormones. GLP-1 and GLP-2 were shown to have pleiotropic effects in intestinal and pancreatic diseases.

Objective

We aimed to investigate the activities of GLP-1 and GLP-2 on nociception and inflammation in mice, involving their actions on serotonergic, nitrergic, and opioidergic systems.

Methods

Antinociceptive and anti-inflammatory activities of intraperitoneally injected GLPs were evaluated in hotplate latency test, formalin-induced behavioral, and paw edema tests. Ondansetron, a selective 5-HT3 receptor antagonist; L-NAME, a NOS inhibitor; and naloxone, an opioid antagonist were injected to determine the mechanisms of antinociception and anti-inflammation. We also measured blood glucose levels and performed rotarod test in order to evaluate whether the hypoglycemic effect of GLP compounds or alterations in locomotor activity may affect the latency in hotplate test and activity in formalin test.

Results

GLP-1 (0.2 mg/kg) and GLP-2 (0.05, 0.2 mg/kg) significantly increased pain threshold. GLP-1 (0.2 mg/kg) and GLP-2 (0.05, 0.1, 0.2 mg/kg) significantly decreased formalin-induced licking and shaking behaviors. GLP-1 or GLP-2 showed no significant inhibitory action on formalin-induced swelling in paws of mice. Antinociceptive actions of GLP-1 and GLP-2 were significantly decreased with ondansetron and naloxone, and paw shaking behavior significantly increased with naloxone. GLP-1 and GLP-2 did not impair rotarod performance, and did not cause a significant hypoglycemic effect in our normoglycemic mice after rotarod test.

Conclusion

These finding indicated that the antinociceptive and anti-inflammatory effect of GLP-1 was related to opioidergic system. Antinociceptive effect of GLP-2 was partially related to 5-HT3 serotonergic or opioidergic system in hotplate test. However, the anti-inflammatory effect of GLP-2 was not directly related to 5-HT3, NO or opioids.

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Funding

This study was supported financially by the Karadeniz Technical University Scientific Research Projects, Turkey.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Avşar Kampusu, Onikişubat, Kahramanmaraş, Turkey

    Duygun Altıntaş Aykan

  2. Department of Pharmacology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

    Murat Kesim

  3. Department of Histology and Embryology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

    Beyza Ayan

  4. Department of Physiology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

    Ayşegül Kurt

Authors
  1. Duygun Altıntaş Aykan
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  2. Murat Kesim
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  3. Beyza Ayan
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  4. Ayşegül Kurt
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Corresponding author

Correspondence to Duygun Altıntaş Aykan.

Ethics declarations

The study was carried out at Karadeniz Technical University Medical Faculty, Medical Pharmacology Department. Local ethics committee approved the study (Ethics Committee File No: 2015/44, Approval date: 15/12/2015).

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The authors declare that there is no conflict of interest.

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Aykan, D.A., Kesim, M., Ayan, B. et al. Anti-inflammatory and antinociceptive activities of glucagon-like peptides: evaluation of their actions on serotonergic, nitrergic, and opioidergic systems. Psychopharmacology 236, 1717–1728 (2019). https://doi.org/10.1007/s00213-018-5154-7

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  • DOI: https://doi.org/10.1007/s00213-018-5154-7

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