Critical interactions between opioid and cannabinoid receptors during tolerance and physical dependence development to opioids in the murine gastrointestinal tract: proof of concept.

Autor: Szymaszkiewicz A; Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland., Świerczyński M; Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland., Talar M; Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland., Polepally PR; Department of Biomolecular Sciences and Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, MS, USA., Zjawiony JK; Department of Biomolecular Sciences and Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, MS, USA., Fichna J; Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland., Zielińska M; Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland. marta.zielinska@umed.lodz.pl.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2021 Aug; Vol. 73 (4), pp. 1147-1154. Date of Electronic Publication: 2021 Jun 16.
DOI: 10.1007/s43440-021-00291-7
Abstrakt: Introduction: Tolerance (TOL) and physical dependence (PD) constitute important limitations of opioid therapy. The aim of our study was to validate research tools to investigate TOL and PD and to characterize the interactions between opioid (OR) and cannabinoid (CB) receptors in these processes in the GI tract.
Methods: TOL was assessed through the comparison of morphine ability to inhibit electrically evoked smooth muscles contractility in the mouse ileum that was previously incubated with/without morphine for 1 h. To evaluate the PD, the ileum was incubated with morphine for 10 min, then challenged with naloxone to induce withdrawal response (WR). The OR/CB interactions were evaluated using mixed agonist (PR-38) and AM-251 (CB1 antagonist).
Results: The inhibitory effect of morphine on ileal contractions was weaker in tissue incubated with this opioid than in tissue incubated without opioid. The opposite was noted for PR-38. In tissues exposed to morphine, but not to PR-38, naloxone induced a WR. The blockage of CB1 receptors with AM-251 before the addition of PR-38 resulted in a naloxone-induced WR.
Conclusion: The co-activation of OR and CB reduced development of TOL and PD to opioids in the mouse GI tract and mixed OR/CB agonists are promising alternative to currently used opioid drugs.
(© 2021. The Author(s).)
Databáze: MEDLINE
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