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LSA Fellows 2

 

Project title: Functional selectivity of opioids at the µ-opioidreceptor: examining the role of phospholipase D2

Projectleader: Prof. Dr. Thomas Koch

 

Thomas Koch

Morphine has long since been valued for its sedating and pain reducing effect but it also causes addiction in patients and must be given in elevated doses over time to preserve effectiveness due to a tolerance effect that sets in. The team of scientist surrounding Dr. Thomas Koch at the Institute for pharmacology and toxicology is studying how and why a tolerance to opiates including morphine is obtained when chronically induced and if there are possible ways of preventing this effect. They have found that different types of opiate substances can affect the same type of receptor in various ways: some opiates such as morphine cause the receptors to shut off in long term treatment and they continue to rest in this state, causing elevated levels of tolerance. Other substances cause an internalization of the receptors, where they are replaced in the membrane and are then available again to perform their task. This mechanism called receptor-endocytosis counteracts tolerance development.

The scientists were able to prove in cell cultures that apart from the commonly used endorphins, other clinically used opiates such as Fentanyl, Piritramid, and Sufentanil can also cause receptor-endocytosis. They found that opiates with elevated endocytoical potential lead to slower tolerance development in cell models. "Due to this negative correlation between endocytoical potential and the resulting level of tolerance observed, the conclusion could be obtained that these substances are better suited for long term therapy" states Dr. Koch. "However, the human body initiates an array of countermeasures on the cellular level as a result of the missing shutdown of the receptors, which can lead to a higher level of substance addiction." Therefore, further in vivo testing is needed to conclude whether endocytoical agonists are really better suited for long term therapy.

Uni Magdeburg als Standort neurowissenschaftlicher Spitzenforschung gestärkt

Deutsche Forschungsgemeinschaft bewilligt Fortsetzung des Sonderforschungsbereichs 1436

Magdeburger Universitätsspitze nimmt gemeinsame Arbeit auf

Rektor Jens Strackeljan startet mit zwei neuen Prorektorinnen in die vierte Amtszeit

Professor Hans-Jochen Heinze bleibt für weitere sechs Jahre im Amt des Ärztlichen Direktors des Universitätsklinikums Magdeburg

Der Aufsichtsrat des Universitätsklinikums Magdeburg hat die Wiederbestellung von Prof. Dr. med. Hans-Jochen Heinze als Ärztlichen Direktor des Universitätsklinikums Magdeburg für weitere sechs Jahre beschlossen.

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LIN Leibniz Institute for Neurobiology Magdeburg


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