Researcher:
Orer, Hakan S.

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Faculty Member

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Hakan S.

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Orer

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Orer, Hakan S.
Orer, Hakan Sedat

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2015 - 201962020 - 20222

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    5-hydroxytryptamine does not reduce sympathetic nerve activity or neuroeffector function in the splanchnic circulation
    (Elsevier, 2015) Darios, Emma S.; Barman, Susan M.; Morrison, Shaun F.; Davis, Robert P.; Seitz, Bridget M.; Burnett, Robert; Watts, Stephanie W.; N/A; Orer, Hakan S.; Faculty Member; School of Medicine; 53477
    Infusion of 5-hydroxytryptamine (5-HT) in conscious rats results in a sustained (up to 30 days) fall in blood pressure. This is accompanied by an increase in splanchnic blood flow. Because the splanchnic circulation is regulated by the sympathetic nervous system, we hypothesized that 5-HT would: 1) directly reduce sympathetic nerve activity in the splanchnic region; and/or 2) inhibit sympathetic neuroeffector function in splanchnic blood vessels. Moreover, removal of the sympathetic innervation of the splanchnic circulation (celiac ganglionectomy) would reduce 5-HT-induced hypotension. In anaesthetized Sprague-Dawley rats, mean blood pressure was reduced from 101 ± 4 to 63 ± 3 mm Hg during slow infusion of 5-HT (25 μg/kg/min, i.v.). Pre- and postganglionic splanchnic sympathetic nerve activity were unaffected during 5-HT infusion. In superior mesenteric arterial rings prepared for electrical field stimulation, neither 5-HT (3, 10, 30 nM), the 5-HT1B receptor agonist CP 93129 nor 5-HT1/7 receptor agonist 5-carboxamidotryptamine inhibited neurogenic contraction compared to vehicle. 5-HT did not inhibit neurogenic contraction in superior mesenteric venous rings. Finally, celiac ganglionectomy did not modify the magnitude of fall or time course of 5-HT-induced hypotension when compared to animals receiving sham ganglionectomy. We conclude it is unlikely 5-HT interacts with the sympathetic nervous system at the level of the splanchnic preganglionic or postganglionic nerve, as well as at the neuroeffector junction, to reduce blood pressure. These important studies allow us to rule out a direct interaction of 5-HT with the splanchnic sympathetic nervous system as a cause of the 5-HT-induced fall in blood pressure. © 2015 Elsevier B.V. All rights reserved.
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    Phase Ia/Ib study of RS-0139, a novel tumor-targeted delivery of docetaxel, in patients with recurrent, locally advanced, or metastatic non-small cell lung cancer (NSCLC)
    (Elsevier, 2022) Nomak, G.; Oksuzoglu, B.; Senturk, R.; Eralp, Y.; Nomak, H.; Sanyal, R.; N/A; Orer, Hakan S.; Yumuk, Perran Fulden; Faculty Member; Other; School of Medicine; School of Medicine; 53477; N/A
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    Overview of the anatomy, physiology, and pharmacology of the autonomic nervous system
    (Wiley, 2016) Wehrwein, Erica A.; Barman, Susan M.; N/A; Orer, Hakan S.; Faculty Member; School of Medicine; 53477
    Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system.
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    5-HT causes venodilatation to reduce blood pressure in the rat
    (Karger, 2016) Seitz, Bridget M.; Krieger-Burke, Theresa; Darios, Emma S.; Thompson, Janice M.; Watts, Stephanie W.; N/A; Orer, Hakan S.; Faculty Member; School of Medicine; 53477
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    IUBMB/PSBMB 2019 conference/plenary: mentoring in postgraduate training and the role of organization for PhD education in health sciences in European system
    (Wiley, 2020) N/A; N/A; Orer, Hakan S.; Faculty Member; School of Medicine; 53477
    A vibrant and sustainable research environment is essential to establish a thriving PhD program. Organization for PhD Education in Health Sciences in European System, a European platform to promote best practices in PhD education in health sciences, published a guideline entitled "Best Practices for PhD Training." The guideline includes comprehensive recommendations and suggestions on different components of the PhD program, of which supervision is an essential one. A working supervisor-student relationship based on mutual respect, responsibility, and participation is essential for the success of a PhD thesis. Supervisors should be active researchers and receive training to develop their supervising skills. They serve as role models in academic life, both scientifically and ethically. The appointment of a co-supervisor, besides the principal one, is strongly encouraged not only to increase the efficiency in monitoring the student progression but also to defuse interpersonal conflicts. Institutional regulations should include the duties and responsibilities of the supervisor. A contract prepared by the institution and signed by the supervisor and the student could help specify the task and may serve as a starting point. In case of a conflict, grievance mechanisms also need to be clear and explicit. Supervisors ought to assist the career development of the students and guide them to become independent researchers. Unfortunately, different surveys showed that there is widespread discontent among the students about their supervisors. Performance pressure on both students and supervisors create enormous tension. Students feel stressed about their career prospects. Institutional policies should consider these stress points to enhance the wellbeing of students as well as the faculty.
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    5-HT causes splanchnic venodilation
    (Amer Physiological Soc, 2017) Seitz, Bridget M.; Krieger-Burke, Teresa; Darios, Emma S.; Thompson, Janice M.; Fink, Gregory D.; Watts, Stephanie W.; N/A; Orer, Hakan S.; Faculty Member; School of Medicine; 53477
    Serotonin [5-hydroxytryptamine (5-HT)] causes relaxation of the isolated superior mesenteric vein, a splanchnic blood vessel, through activation of the 5-HT7 receptor. As part of studies designed to identify the mechanism(s) through which chronic (>= 24 h) infusion of 5-HT lowers blood pressure, we tested the hypothesis that 5-HT causes in vitro and in vivo splanchnic venodilation that is 5-HT7 receptor dependent. In tissue baths for measurement of isometric contraction, the portal vein and abdominal inferior vena cava relaxed to 5-HT and the 5-HT1/7 receptor agonist 5-carboxamidotryptamine; relaxation was abolished by the 5-HT7 receptor antagonist SB-269970. Western blot analyses showed that the abdominal inferior vena cava and portal vein express 5-HT7 receptor protein. In contrast, the thoracic vena cava, outside the splanchnic circulation, did not relax to serotonergic agonists and exhibited minimal expression of the 5-HT7 receptor. Male SpragueDawley rats with chronically implanted radiotelemetry transmitters underwent repeated ultrasound imaging of abdominal vessels. After baseline imaging, minipumps containing vehicle (saline) or 5-HT (25 mu g.kg(-1).min(-1)) were implanted. Twenty-four hours later, venous diameters were increased in rats with 5-HT-infusion (percent increase from baseline: superior mesenteric vein, 17.5 +/- 1.9; portal vein, 17.7 +/- 1.8; and abdominal inferior vena cava, 46.9 +/- 8.0) while arterial pressure was decreased (similar to 13 mmHg). Measures returned to baseline after infusion termination. In a separate group of animals, treatment with SB-269970 (3 mg/kg iv) prevented the splanchnic venodilation and fall in blood pressure during 24 h of 5-HT infusion. Thus, 5-HT causes 5-HT7 receptor-dependent splanchnic venous dilation associated with a fall in blood pressure. NEW & NOTEWORTHY This research is noteworthy because it combines and links, through the 5-HT7 receptor, an in vitro observation (venorelaxation) with in vivo events (venodilation and fall in blood pressure). This supports the idea that splanchnic venodilation plays a role in blood pressure regulation.
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    Fourth-year rational pharmacotherapy clerkship at Koc University School of Medicine
    (Springer Heidelberg, 2019) N/A; Gülmez, Sinem Ezgi; Özcan, Gülnihal; Orer, Hakan S.; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; 281312; 185014; 53477
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    PublicationOpen Access
    Institutional policy to implement bioethics principles in graduate education
    (Wiley, 2018) Department of Molecular Biology and Genetics; Orer, Hakan S.; Faculty Member; Department of Molecular Biology and Genetics; School of Medicine; 53477