NDLI: Up-Regulation of 5-HT2B Receptor Density and Receptor-Mediated Glycogenolysis in Mouse Astrocytes by Long-Term Fluoxetine Administration

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Up-Regulation of 5-HT2B Receptor Density and Receptor-Mediated Glycogenolysis in Mouse Astrocytes by Long-Term Fluoxetine Administration

Content Provider	Springer Nature Link
Author	Kong, Ebenezer K. C. Peng, Liang Chen, Ye Yu, Albert C. H. Hertz, Leif
Copyright Year	2002
Abstract	The effects were studied of short-term (1 week) versus long-term (2-3 weeks) fluoxetine treatment of primary cultures of mouse astrocytes, differentiated by treatment with dibutyryl cyclic AMP. From previous experiments it is known that acute treatment with fluoxetine stimulates glycogenolysis and increases free cytosolic Ca$^{2+}$ concentration ([Ca$^{2+}$]$_{i}$]) in these cultures, whereas short-term (one week) treatment with 10 μM down-regulates the effects on glycogen and [Ca$^{2+}$]$_{i}$, when fluoxetine administration is renewed (or when serotonin is administered). Moreover, antagonist studies have shown that these responses are evoked by activation of a 5-HT$_{2}$ receptor that is different from the 5-HT$_{2A}$ receptor and therefore at that time tentatively were interpreted as being exerted on 5-HT$_{2C}$ receptors. In the present study the cultures were found by RT-PCR to express mRNA for 5-HT$_{2A}$ and 5-HT$_{2B}$ receptors, but not for the 5-HT$_{2C}$ receptor, identifying the 5-HT$_{2}$ receptor activated by fluoxetine as the 5-HT$_{2B}$ receptor, the most recently cloned 5-HT$_{2}$ receptor and a 5-HT receptor known to be more abundant in human, than in rodent, brain. Both short-term and long-term treatment with fluoxetine increased the specific binding of [$^{3}$H]mesulergine, a ligand for all three 5-HT$_{2}$ receptors. Long-term treatment with fluoxetine caused an agonist-induced up-regulation of the glycogenolytic response to renewed administration of fluoxetine, whereas short-term treatment abolished the fluoxetine-induced hydrolysis of glycogen. Thus, during a treatment period similar to that required for fluoxetine's clinical response to occur, 5-HT$_{2B}$-mediated effects are initially down-regulated and subsequently up-regulated.
Starting Page	113
Ending Page	120
Page Count	8
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	27
Issue Number	1-2
e-ISSN	15736903
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2002-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Neurosciences Neurology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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