The serotonin transporter (SERT) and the control of circulating serotonin in teleost fish

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Serotonin is a neurotransmitter most commonly known for its role in depression. In mammals, serotonin can also cause the constriction of blood vessels, altering blood flow to organs throughout the body. Mammalian serotonin transporters in blood platelets remove serotonin from the blood plasma, thereby controlling serotonin's effect on blood vessels. In fishes as in mammals, serotonin levels within the blood plasma are low and elevation of circulating serotonin results in the constriction of blood vessels. However, in contrast to mammals, significant levels of serotonin have not been found within fish blood cells and it is not known how circulating serotonin levels are regulated in fish. This project will fill that gap by characterizing the serotonin transporter's role in controlling circulating levels of serotonin, and thus blood pressure and flow, in fish. Fish will be tested in water with normal oxygen levels, and in low-oxygen conditions when controlling blood flow to active tissues and organs such as the gills is most important. It is expected that this project will reveal the role of serotonin and the serotonin transporter in the control of blood pressure and flow in fish, contributing significantly to the field of cardiovascular physiology. Results may also help to answer existing questions about serotonin's role in blood flow control in mammals. The project will educate and expose underrepresented youth to science, enhance the participation of women and minorities in science, and strengthen collaborative partnerships. The role of the serotonin transporter (SERT) in controlling circulating levels of serotonin (or hydroxytryptamine, 5-HT) and, consequently, vascular resistance, in the Gulf toadfish (Opsanus beta) will be determined under normoxic and hypoxic conditions. Three questions will be addressed: (1) What are the tissue distribution, transport kinetics, and pharmacological sensitivity of a teleost SERT compared to SERT of other vertebrates? (2) What is the role of systemic SERT in the control of circulating 5-HT? (3) What is the role of branchial SERT in the control of circulating 5-HT? The answers to these questions will support the central hypothesis that SERT plays an integral role in controlling circulating 5-HT and, as a result, vascular resistance, blood pressure, and blood flow in teleost fish. Advanced techniques, including fluorescent neurotransmitter imaging probes, will be applied to investigate SERT function at the cellular level. The research will reveal organs, such as the heart, and cell types, such as gill neuroepithelial cells, that are active contributors to 5-HT homeostasis. The potential role of SERT in controlling circulating 5-HT is important because uncontrolled circulating 5-HT levels would lead to an undesirable vasoconstriction of the gill and detrimental reductions in oxygen uptake, an effect that could reduce hypoxia tolerance and limit survival. Project outcomes will also contribute to understanding the possible implications of SERT activation or desensitization with environmental perturbations such as hypoxia and pharmaceutical exposure. The project's educational and outreach impacts include engaging underrepresented youth in marine science and enhancing the participation of women and minorities in science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.