Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Hartl, N.
The lipid receptor GPR55, its ligands and the anti-obesity agent Rimonabant
[ Diplomarbeit ] Medical University of Graz; 2010. pp. 60
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Marsche Gunther
- Waldhoer Maria
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- Abstract:
- Abstract This diploma thesis reports on the recently de-orphanized lipid receptor GPR55, its ligands and which effects they cause, as well as the anti-obesity drug Rimonabant. The effects of cannabinoids in the human body are mediated by several receptors, i.e. the cannabinoid receptor type 1- CB1, the cannabinoid receptor type 2- CB2, the transient receptor potential vanilloid type 1 - TRPV1 and the newly discovered G-protein coupled receptor GPR55. CB1 is located in many tissues in the human body and its psychotropic effects evoked by delta9-tetrahydrocanabinol, also known as 9-THC, by consumption of marijuana are well known. In addition, CB1 is associated with the development of diseases, such as diabetes, drug dependency, metabolic syndrome and obesity. Thus, several pharmaceutical companies investigated the therapeutic effects of CB1 and discovered Rimonabant, an inverse agonist/antagonist of CB1, as an anti-obesity agent. Several clinical trials showed the efficacy of Rimonabant in overweight and obese patients, inducing weight loss and improvement of cardiovascular and diabetic risk factors. Nevertheless, many patients reported about psychiatric adverse events, such as depressive mood, anxiety, depression and even suicidal thoughts. These reports finally resulted in the withdrawal of Rimonabant from the world-wide market in 2008. However, experiments performed with CB1/CB2 knock-out mice revealed that many effects evoked by cannabinoids were not mediated by the two classical cannbinoid receptors, CB1 or CB2, respectively. This receptor was finally identified as the G-protein coupled receptor GPR55 in 1999, but a clear classification of GPR55 to the cannabinoid receptor family is yet premature. GPR55 was found to be expressed in several tissues, such as the brain, testes, adipose tissue, spleen and liver. The pharmacology of GPR55 is still a controversial topic. In my diploma thesis I summarize recent findings on the pharmacology, downstream signalling and cellular effects of this recently de-orphanized lipid receptor GPR55. Moreover, I listed its potential ligands, including endocannabinoids, phytocannabinoids and synthetic ligands, and described which effects they cause on a molecular and physiological level in both mice and humans.