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Stimulation of Cloned Human Serotonin 5‐HT 1Dβ Receptor Sites in Stably Transfected C6 Glial Cells Promotes Cell Growth
Author(s) -
Pauwels Petrus J.,
Wurch Thierry,
Amoureux MarieClaude,
Palmier Christiane,
Colpaert Francis C.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66010065.x
Subject(s) - transfection , stimulation , serotonin , 5 ht receptor , microbiology and biotechnology , receptor , neuroscience , chemistry , biology , cell culture , biochemistry , genetics
The involvement of serotonin 5‐HT 1Dβ receptor sites was investigated in the growth of rat C6 glial cells permanently transfected with a gene encoding a human 5‐HT 1Dβ receptor. The 5‐HT receptor identity of control and transfected C6 glial/5‐HT 1Dβ cells was determined by reverse transcription‐polymerase chain reaction using primers specific for rat 5‐HT 1A , rat 5‐HT 1B , rat 5‐HT 1Dα , human 5‐HT 1Dβ , and rat 5‐HT 2A receptor genes. Constitutive mRNA for 5‐HT 2A receptors was present in control and transfected C6 glial/5‐HT 1Dβ cells, whereas mRNA for 5‐HT 1Dβ receptor sites was only present in the transfected C6 glial/5‐HT 1Dβ cell line. 5‐HT inhibited forskolin‐stimulated cyclic AMP formation and promoted cell growth, in contrast to the absence of any measurable effect in pcDNA3 plasmid‐transfected and nontransfected C6 glial cells. The 5‐HT effects could be mimicked by sumatriptan (EC 50 = 44–76 n M ) and were totally and partially blocked by methiothepin (IC 50 = 9 n M ) and GR 127,935 {2′‐methyl‐4′‐(5‐methyl[1,2,4]oxadiazol‐3‐yl)‐biphenyl‐4‐carboxylic acid [4‐methoxy‐3‐(4‐methylpiperazin‐1‐yl)phenyl]amide; IC 50 = 97 p M }, respectively. No effect on cell growth was measured with the 5‐HT 2 receptor agonist DOI [1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane; 10 µ M ], suggesting that 5‐HT 2A receptors are not involved in the 5‐HT‐stimulated C6 glial/5‐HT 1Dβ cell growth. Dibutyryl‐cyclic AMP (0.3 m M )‐treated cultures did not show sumatriptan‐promoted cell growth, indicating an inhibitory role for cyclic AMP in the cell growth mediated by 5‐HT 1Dβ receptor sites. In conclusion, 5‐HT promotes cell proliferation in transfected C6 glial/5‐HT 1Dβ cells by stimulation of 5‐HT 1Dβ receptor sites. These receptor sites may be a new target to modulate the growth of tumor cells.