Sherine AbdelmissihCairo University, Egypt
Title: The Aryl hydrocarbon receptors as potential targets in drug addiction
The aryl hydrocarbon receptors (AhRs) are transcription factors and members of the basic-helix-loop-helix (bHLH) family. They exist as part of a cytoplasmic complex comprising the heat shock protein 90, p23 and X-associated protein 2, which seem to perpetuate the short AhRs life span (1-2 hours). Upon ligand binding, the inactive complex translocates to the nucleus, assisted by pendulin, followed by dissociation of the AhRs from the inactive complex to be activated by combining with the aryl hydrocarbon nuclear translocator (AhNT). The AhRs/AhNT heterodimer binds to the dioxin response element (DRE) enhancer, leading to enhanced expression of cytochrome p450 (CYP450) genes, with subsequent alteration of drugs and xenobiotics metabolism. Alcohols might mediate compensatory induction of CYP450 enzymes to withstand the effects of chronic alcoholism. Opioids analgesics are known substrates for CYP450 enzymes, yielding not only inactive, but also active metabolites, and which upregulation was also involved in tolerance to opioids. The toxicity of illicit drugs such as cocaine has been attributed to induced metabolism by CYP450, meanwhile components of another cannabis can induce CYP450. CYP450 has been implicated in the synthesis of dopamine from tyramine, a well-established mediator of addiction. Dopamine has recently been identified as an AhR agonist and CYP450 inducer. So, AhRs as potential targets of drug addiction will be discussed, in terms of CYP450 upregulation.
Sherine Abdelmissih has completed her M.D. at the age of 40 years from Cairo University, Egypt. She is a lecturer in Medical Pharmacology Department, Faculty of Medicine Kasr Al-Ainy, Cairo University, Egypt, since 2016. She is a Subinvestigator in Clinical Trial Research Center, Medical Pharmacology Department, Faculty of Medicine Kasr Al-Ainy, Cairo University, Egypt, since 2017. She is a member at European College of Neuropsychopharmacology (ECNP), member of British Pharmacological Society (BPS) and member of the American Academy of Sleep Medicine. She has published 3 original research articles, one review and one book chapter. She has reviewed 13 published articles.