Promotion of cell growth by stimulation of cloned human 5-HT1Dreceptor sites in transfected C6-glial cells is highly sensitive to intrinsic activity at 5-HT1Dreceptors
✍ Scribed by Petrus J. Pauwels; Thierry Wurch; Christiane Palmier; Francis C. Colpaert
- Publisher
- Springer-Verlag
- Year
- 1996
- Tongue
- English
- Weight
- 921 KB
- Volume
- 354
- Category
- Article
- ISSN
- 0028-1298
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✦ Synopsis
5-Hydroxytryptamine (serotonin, 5-HT), essentially known as a neurotransmitter and vasoactive agent, also functions as a mitogen in various cell types through several different second messenger systems. Stimulation of cloned human 5-HTm receptor sites by sumatriptan in stably transfected rat C6-glial/5-HTID cells promotes cell growth (Pauwels et al. (1996) Naunyn-Schmiedeberg's Arch Pharmacol 353: 144-156).
In the present study, the pharmacology of this growth response was investigated using a broad series of 5-HT receptor ligands. The data were compared with the responses obtained by measuring inhibition of forskolin-stimulated cAMP formation. 5-HT (EC5o: 25 nM) promoted cell growth of C6-glial/5-HT1D cells, and this in contrast to the absence of any measurable effect in pcDNA3-plasmid transfected and non-transfected C6-glial cells. The 5-HT effect could be mimicked by the following compounds (ECs0 in nM): zolmitriptan (0.41), 2'-methyl-4'-(5-methyl[1,2,4] oxadiazol-3-yl)biphenyl-4-carboxylic acid [4-methoxy-3-(4methylpiperazin-l-yl)phenylJamide (GR 127,935; 0.86), naratriptan (0.92), metergoline (1.9), sumatriptan (2.9), (N,N-dimethyl-2-[5-(1,2,4-triazol-l-ylmethyl)-lH-indol-3-ylJethylamine (MK-462; 3.0), and R(+)-8-(hydroxy-2-(di-n-propylamino)tetralin (R( + )-8-OH-DPAT; 30.7). These ECso-values correspond to the compounds binding affinities at the human 5-HTtD receptor site and, with the exception of GR 127,935 and metergoline, also to the ECs0-values found by measuring over 5 rain inhibition of forskolin (100 gM)-stimulated cAMP formation. Prolonged exposure of GR 127,935 (3 h) and metergoline (30 min) to cells yielded ECso values in the cAMP assay more close to those measured in the mitogenic response. The growth response to sumatriptan, 5-HT, GR 127,935 and metergoline was blocked by P. J. Pauwels (Eg3) • T.