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Endogenous and Exogenous Melatonin Exposure Attenuates Hepatic MT1 Melatonin Receptor Protein Expression in Rat

Department of Anesthesiology and Intensive Care Medicine, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany
Department of Anesthesiology, Critical Care and Pain Medicine, Saarland University Hospital, 66424 Homburg, (Saar), Germany
Department of Urology, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081 Ulm, Germany
Department of Anesthesiology, University Hospital Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(9), 408;
Received: 19 August 2019 / Revised: 13 September 2019 / Accepted: 15 September 2019 / Published: 18 September 2019
Melatonin receptors are highly relevant for the hepatoprotective effects of the pineal hormone melatonin after experimental hemorrhagic shock in rats. In this study, we sought to determine the spatial expression pattern and a putative regulation of two melatonin receptors, membrane bound type 1 and 2 (MT1 and MT2), in the liver of rats. In a male rat model (Sprague Dawley) of hemorrhage and resuscitation, we investigated the gene expression and protein of MT1 and MT2 in rat liver by utilizing real-time quantitative polymerase chain reaction, a western blot analysis, and immunohistochemistry. Plasma melatonin content was measured by an enzyme-linked immunosorbent assay. Male rats underwent hemorrhage and were resuscitated with shed blood and a Ringer’s solution (n = 8 per group). After 90 min of hemorrhage, animals were given vehicle, melatonin, or ramelteon (each 1.0 mg/kg intravenously). Sham-operated controls did not undergo hemorrhage but were treated likewise. Plasma melatonin was significantly increased in all groups treated with melatonin and also after hemorrhagic shock. Only MT1, but not the MT2 messenger ribonucleic acid (mRNA) and protein, was detected in the rat liver. The MT1 protein was located in pericentral fields of liver lobules in sham-operated animals. After hemorrhagic shock and treatment with melatonin or ramelteon, the hepatic MT1 protein amount was significantly attenuated in all groups compared to sham controls (50% reduction; p < 0.001). With respect to MT1 mRNA, no significant changes were observed between groups (p = 0.264). Our results indicate that both endogenous melatonin exposure from hemorrhagic shock, as well as exogenous melatonin and ramelteon exposure, may attenuate melatonin receptors in rat hepatocytes, possibly by means of desensitization. View Full-Text
Keywords: melatonin receptor; liver; spatial distribution; melatonin; ramelteon; shock melatonin receptor; liver; spatial distribution; melatonin; ramelteon; shock
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Mathes, A.M.; Heymann, P.; Ruf, C.; Huhn, R.; Hinkelbein, J.; Volk, T.; Fink, T. Endogenous and Exogenous Melatonin Exposure Attenuates Hepatic MT1 Melatonin Receptor Protein Expression in Rat. Antioxidants 2019, 8, 408.

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