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Understanding the downstream actions of antidepressants that selectively increase serotonin (5-HT)I have focused my efforts on answering two very specific questions relevant to understanding the mechanism of action of antidepressants that increase serotonin (5-HT): 1) Which cellular signals are modulated by receptors for 5-HT. and 2) why are there so many receptors for 5-HT (at least 16)? With regards to the first question. I am most interested in identifying coupling of receptors to signals known to activate protein synthesis. Changes in neuronal protein synthesis are induced by treatment with antidepressants. and are thought to mediate the long-term effects of antidepressants. With regards to the second focus of my lab. receptors for 5-HT are currently grouped into 7 families. based in part. on their coupling to intracellular signals. My hypothesis has been that although all of the receptors within a family couple to the particular signal required for that classification (e.g. cyclic AMP) they may not all couple to other individual signals. Selected PublicationsJohnson-Farley NN, Patel K, Kim D, Cowen DS. (2007) Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal survival in hippocampal cultures. Brain Res. 1154:40-9. Cowen DS. (2007) Serotonin and neuronal growth factors - a convergence of signaling pathways. J Neurochem. 101(5):1161-71. Johnson-Farley NN, Travkina T, Cowen DS. (2006) Cumulative activation of akt and consequent inhibition of glycogen synthase kinase-3 by brain-derived neurotrophic factor and insulin-like growth factor-1 in cultured hippocampal neurons. J Pharmacol Exp Ther. 316(3):1062-9. Duann P, Ho TY, Desai BD, Kapoian T, Cowen DS, Lianos EA. (2005) Mesangial cell apoptosis induced by stimulation of the adenosine A3 receptor: signaling and apoptotic events. Cowen D.S.. Johnson-Farley N.N.. and Travkina T. (2005) 5-HT1A receptors couple to activation of Akt. but not extracellular-regulated kinase (ERK). in cultured Hippocampal Neurons. J. Neurochem. 93(4):910-7. Johnson-Farley N.N.. Kertesy S.B.. Dubyak G.R.. and Cowen D.S. (2005) Enhanced activation of neuroprotective Akt and extracellular-regulated kinase (ERK) pathways by simultaneous occupancy of Gq-coupled 5-HT2A receptors and Gs-coupled 5-HT7A receptors in PC12 Cells. J. Neurochem. 92: 72-82. Lin S.L.. Johnson-Farley N.N.. Lubinsky D.R.. and Cowen D.S. (2003) Coupling of neuronal 5-HT7 receptors to activation of extracellular-regulated kinase through a protein kinase A-independent pathway that can utilize Epac. J. Neurochem. 87: 1076 -1085. Quinn J.C.. Johnson-Farley N.N.. Yoon J.Y.. and Cowen D.S. (2002) Activation of extracellular-regulated kinase by 5-HT2A receptors in PC12 cells is protein kinase C-independent and requires Calmodulin and Tyrosine Kinases. J. Pharmacol. Exp. Ther. 303: 746-752. Errico. M.. Crozier. R.. Plummer. M. R. and Cowen. D. S. (2001) 5-HT7 receptors activate the mitogen-activated protein kinase ERK in cultured hippocampal neurons. Neuroscience. 102: 361-367. Hsu. E. H.. Lochan. A. C. and Cowen. D. S. (2001) Activation of Akt1 by human 5-HT1B receptors is sensitive to inhibitors of MEK. J. Pharm. Exp. Ther. 298: 825-832. Lione. A. M.. Errico. M.. Lin. S. L. and Cowen. D. S. (2000) Activation of extracellular signal-regulated kinase (ERK) and Akt by human 5-HT1B receptors in transfected BE(2)-C neuroblastoma cells is inhibited by RGS4. J. Neurochem. 75: 934-938. |
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