Prof. Elif Cadirci
Ataturk University, Turkiye
Dr. Elif ÇADIRCI was born in Yusufeli in 1982. She graduated from Atatürk University Faculty of Pharmacy with a degree in 2004. She completed her doctorate in Atatürk University Faculty of Medicine, Department of Medical Pharmacology in 2009. In 2011, he worked as a postdoctoral researcher at Oxford University School of Medicine, Department of Pharmacology (England). He became assistant professor in 2010, associate professor in 2012, and full professor in 2018.
Dr. ÇADIRCI is a member of the Turkish Pharmacists Association and the Turkish Pharmacology Association. She served as a board member and treasurer of the Turkish Pharmacology Association between 2016-2020. He is currently the section editor of "The Eurasian Journal of Medicine" and a member of the TÜBİTAK Health Sciences Research Support Group Executive Board. Throughout her career, Elif ÇADIRCI has been awarded by the Atatürk University Rectorate in the fields of Effective Article, Patent, Best Scientific Research Project, Best Thesis Project in different years. In 2004, she was awarded the Special Student Incentive Award by the Marmara University Faculty of Pharmacy Alumni Association. ÇADIRCI was awarded the ROCHE-osteoporosis second prize in 2008, the Turkish Pharmacists Association Pharmacy Academy Encouragement Award in 2012, the Turkish Pharmacology Association R. Kazım Türker Young Pharmacologist Encouragement Award in 2013, and the Turkish Academy of Sciences Young Scientist Incentive Award in 2014 (TÜBA-GEBİP). She was awarded the TÜBİTAK Encouragement Award in the Field of Health Sciences in 2020 and Dr. Nejat F. Eczacıbaşı Medical Incentive Award and the Science Heroes Association Scientist of the Year Award and the METU-Parlar Foundation Research Incentive Award in 2021. She received the Turkish Pharmacists Association Pharmacy Academy Science Award in 2023. Prof. Dr. Elif ÇADIRCI works on the UTR2 receptors and physiopathological roles of serotonin 5-HT7 and urotensin, sepsis, sepsis physiopathology and new treatment strategies, inflammation and related diseases, gastric ulcer, boron mineral and its use in bone health. She is currently the Head of the Department of Medical Pharmacology at Atatürk University Faculty of Medicine and the Coordinator of the Project Office of Ataturk University.
5-HT7 receptors as new therapeutic targets
Prof. Dr. Elif ÇADIRCI
Atatürk University, Faculty of Medicine, Department of Pharmacology
Serotonin (5-hydroxytryptamine, 5-HT) is a biological amine and the presence of 14 different receptor subtypes makes it easy to explain the broad physiological effects of this neurotransmitter (1). Serotonin plays a role in the pathophysiology of many diseases such as depression, anxiety, circadian rhythm, schizophrenia, bulimia nervosa, anorexia nervosa, asthma, inflammation, etc. It is known that chronic inflammation has a vital role in tumor carcinogenesis and tumor development (2). 5-HT7 is also one of the most recently discovered but least characterized receptors for serotonin. The presence of this receptor was first demonstrated in 1993 by many independent laboratories (3-6). When tissue distribution is investigated, it has been shown in thalamus, hypothalamus, cerebral cortex, hippocampus and amygdala (7-9). In recent years, many studies have been conducted on the functions of these receptors. The effects of 5-HT7 receptors on the central nervous system have been studied in detail, and it has been shown that they play a role in circadian rhythm and (10) thermoregulation (11). It has been claimed that it plays a role in learning and memory functions related to the hippocampus (12, 13) and also contributes to neuroendocrine regulation (14). However, studies on the peripheral expression of these receptors are very limited. In peripheral tissues, 5-HT7 receptor mRNA has been demonstrated in the ileum, spleen, endocrine glands, and arteries. Because of their presence on smooth muscles in the periphery, their possible effects have been investigated and it has been shown to play a role in irritable bowel syndrome (15, 16). It has been shown that these receptors are located in arteries such as pulmonary, coronary arteries and aorta (17, 18). It has been claimed that this effect of 5-HT7 receptors in the relaxation of smooth muscles in the gastrointestinal tract and vascular bed is mediated by adenylate cyclase (19).
The roles of these receptors in inflammatory processes, whose peripheral effects are less studied than their central effects, were studied by our research group (20). It has been shown in our laboratories that 5-HT7 receptors, which are low in healthy tissues in the periphery, increase in conditions such as inflammation (20), sepsis (21), myocardial infarction (22). In these pathologies modeled in experimental animals, the 5-HT7 receptor agonist caused both a decrease in inflammation and an improvement in other parameters. An increase in 5-HT7 receptor mRNA expression has been shown in liver damage induced by different chemicals such as paracetamol, ethanol and carbon tetrachloride, and it has been shown that both the damage and this expression increase regress when a 5-HT7 receptor agonist is applied (23). In the continuation of these studies, the roles of 5-HT7 receptors, which we think are related to the immune system and contribute to pathological events as a defense mechanism of our body, in stomach, breast and prostate (24) cancers were investigated. An increase in the expression of 5-HT7 receptors was observed in these cancers, and a significant anticancer effect was demonstrated in the treatment with a receptor antagonist. Thus, it has been shown that 5-HT7 receptors are involved in the development and treatment of cancer as well as playing a role in many physiological mechanisms in the central nervous system. The expression of these receptors was higher in breast, prostate and gastric cancerous tissues compared to healthy tissues. The increased expression of 5-HT7 receptors in cancer tissues suggested that these receptors may be increased to contribute the bad prognosis in cancer and/or rebound mechanism of the defense system. In our studies, the increase of 5-HT7 receptors in different pathologies and the regression of the pathologies after agonist and/or antagonist administration are very important for the development of alternative treatment methods. In this context, 5-HT7 receptors should be examined in more detail in in vitro, in vivo and clinical studies as new drug targets.
Acknowledgment: These studies were supported by the Scientific and Technological Research Council of Turkey with the projects numbered TÜBİTAK-112S627 and TÜBİTAK-214S006.
Keywords: Serotonin, 5-HT7 receptors, inflammation, sepsis, cancer.
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22. Cinar I, Halici Z, Dincer B, Sirin B, Cadirci E. The role of 5-HT7 receptors on isoproterenol-induced myocardial infarction in rats with high-fat diet exacerbated coronary endothelial dysfunction. Hum Exp Toxicol. 2020;39(8):1005-18.
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24. Cinar I, Sirin B, Halici Z, Palabiyik-Yucelik SS, Akpinar E, Cadirci E. 5-HT7 receptors as a new target for prostate cancer physiopathology and treatment: an experimental study on PC-3 cells and FFPE tissues. Naunyn-Schmiedeberg's archives of pharmacology. 2021;394(6):1205-13.
